更新版肿瘤新辅助治疗病理学响应评分指南 (4/18/2026)
Updated pan-tumor guidelines for scoring neoadjuvant pathologic response: by SITC and INMC
本文发布了关于SITC (Society for Immunotherapy of Cancer) 与 INMC (International Neoadjuvant Melanoma Consortium) 泛肿瘤病理学响应评分与报告的更新版共识指南。
• 指南提供了基于肿瘤大小（≤3 cm 与 >3 cm）的标准化组织送检流程。
对于直径在3厘米及以下的肿瘤或肿瘤床，建议将其整体送检；若肿瘤直径超过3厘米，则至少应沿肿瘤最大径方向切取一个完整的横断面进行包埋，且在条件允许的情况下，应同时切取肿瘤与周围组织交界处的标本。
• 通过对肿瘤成分、坏死情况及退缩程度进行评估，并计算残余存活肿瘤百分比（%RVT），从而对病理学响应进行量化。
针对新辅助治疗的病理学反应，对原发肿瘤及淋巴结成分的量化与评分，应基于残存存活肿瘤、坏死及退缩的百分比进行评估。
• 统一的报告模板有助于确保不同肿瘤类型之间的数据采集具有一致性。
十几位参与的病理学家通过在线讲座接受了关于更新版疗效响应评分标准的培训；随后，他们对来自12种不同肿瘤类型的42份标本进行了评估，依据更新后的标准，对残余存活肿瘤, 坏死及消退程度进行测量分析。此外，研究人员还对参与者进行了问卷调查，以了解他们在应用这一新型疗效评估体系时的使用体验及所面临的挑战。 研究结果显示，采用这一新型“泛肿瘤”评估体系，病理学响应评分标准具有高度的可重复性。在残存存活肿瘤, 坏死及消退程度的测量指标上，参与者之间的相关系数均超过了0.8。亚组分析也证实了这种极强的可重复性，其组内相关系数均在0.86以上。
• 这一方法不仅便于开展跨试验间的比较分析，还有助于确定具有临床意义的 残余存活肿瘤百分比 (%RVT) 阈值。
This article presents updated consensus guidelines from the SITC (Society for Immunotherapy of Cancer) and INMC (International Neoadjuvant Melanoma Consortium) regarding pan-tumor pathological response scoring and reporting.
• The guidelines provide a standardized tissue submission protocol based on tumor size (≤3 cm vs. >3 cm).
For tumors or tumor beds with a diameter of 3 cm or less, submission of the entire specimen is recommended; if the tumor diameter exceeds 3 cm, at least one full cross-section along the maximum tumor dimension should be submitted for embedding, and—where feasible—specimens capturing the interface between the tumor and surrounding tissue should also be obtained.
• Pathological response is quantified through the assessment of tumor cellularity, necrosis, and regression, culminating in the calculation of the percentage of residual viable tumor (%RVT).
Regarding pathological response to neoadjuvant therapy, the quantification and scoring
of primary tumor and lymph node components should be based on the percentages of
residual viable tumor, necrosis, and regression.
• A standardized reporting template facilitates consistent data collection across different tumor types.
Over a dozen participating pathologists received training on the updated response scoring
criteria via online lectures; subsequently, they evaluated 42 specimens representing 12
distinct tumor types, measuring and analyzing the extent of residual viable tumor,
necrosis, and regression in accordance with the revised criteria. Furthermore, the
researchers administered a questionnaire to the participants to gather insights into their
experiences and the challenges encountered while applying this novel response
assessment system. The results demonstrated that, utilizing this new “pan-tumor”
assessment system, the pathological response scoring criteria exhibited high
reproducibility. For the metrics measuring residual viable tumor, necrosis, and regression,
the inter-rater correlation coefficients among participants all exceeded 0.8. Subgroup
analyses further corroborated this robust reproducibility, with intra-class correlation
coefficients consistently exceeding 0.86.
• This methodology not only facilitates comparative analyses across different trials but also aids in establishing clinically meaningful thresholds for %RVT.
参考文献 Reference
Deutsch JS et al. Ann Onc 2026 ; 37 :141
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转移性胰腺癌的化疗联合或不联合医学监护生酮饮食的随机II期试验 (4/12/2026)
A randomized phase II trial of chemotherapy with or without a medically supervised ketogenic diet for metastatic pancreatic cancer
背景：本研究针对既往未接受过治疗的转移性胰腺导管腺癌患者，开展了一项随机II期筛选试验，旨在比较吉西他滨 纳米紫杉醇, 顺铂联合医学监督生酮饮食（MSKD）与联合常规饮食（非MSKD）的疗效。
方法：未接受过治疗的转移性PDAC患者按1:1的比例随机分配至MSKD组或非MSKD组；两组患者均接受吉西他滨, 纳米紫杉醇和顺铂治疗，给药时间为每21天周期的第1天和第8天。MSKD方案由远程医疗团队指导，并依据每日酮体（β-羟基丁酸）水平进行调整，目标β-羟基丁酸水平设定为0.5至3.0 mM。主要终点为无进展生存期，采用单侧α水平0.20进行统计检验。次要终点包括总生存期, 安全性和生活质量。肠道微生物组的变化被列为探索性终点。
结果：总体而言，共有32例患者纳入疗效评估。在MSKD组中，16例患者中有15例达到了营养性生酮状态；达到生酮状态的天数比例中位数为39.4%。MSKD组患者的中位无进展生存期为8.5个月，非MSKD组患者为6.2个月：风险比为0.53（95% CI：0.21-1.37）；单侧 p 值为0.096。MSKD组的中位总生存期为13.7个月，非MSKD组为10.2个月：风险比为0.58（95% CI：0.25-1.37）；单侧 p 值为0.107。所有与MSKD相关的不良事件均为1-2级。各组间≥3级的化疗相关不良事件发生率无显著差异。接受MSKD治疗的患者生活质量未见下降，且其微生物组中多种有益菌群呈现显著富集（p < .05，log倍数变化 ≥ 2）。
结论：MSKD方案在胰腺导管腺癌患者中具有可行性。尽管本研究样本量尚不足以得出确切的临床终点结论，但数据显示，当MSKD与吉西他滨, 纳米紫杉醇及顺铂联合应用时，呈现出改善无进展生存期和总生存期的趋势，且未增加额外毒性或对患者生活质量造成损害。尚需开展更大规模的研究来进一步证实上述发现。
Background: The reseachers conducted a randomized phase II screening trial in previously untreated patients with metastatic pancreatic ductal adenocarcinoma to compare the efficacy of gemcitabine, nab-paclitaxel, and cisplatin combined with a medically supervised ketogenic diet (MSKD) versus a conventional diet (non-MSKD).
Methods: Previously untreated patients with metastatic pancreatic ductal adenocarcinoma were randomized in a 1:1 ratio to either the MSKD group or the non-MSKD group. Patients in both groups received gemcitabine, nab-paclitaxel, and cisplatin, administered on Days 1 and 8 of every 21-day cycle. The MSKD regimen was guided by a telemedicine team and adjusted based on daily ketone (beta-hydroxybutyrate) levels, targeting a beta-hydroxybutyrate range of 0.5 to 3.0 mM. The primary endpoint was progression-free survival, assessed using a one-sided alpha level of 0.20. Secondary endpoints included overall survival, safety, and quality of life. Changes in the gut microbiome were included as an exploratory endpoint.
Results: Overall, 32 patients were included in the efficacy analysis. In the MSKD group, 15 of the 16 patients achieved a state of nutritional ketosis; the median proportion of days spent in ketosis was 39.4%. The median progression-free survival was 8.5 months in the MSKD group versus 6.2 months in the non-MSKD group (hazard ratio [HR]: 0.53; 95% CI: 0.21–1.37; one-sided p = 0.096). The median overall survival was 13.7 months in the MSKD group versus 10.2 months in the non-MSKD group (HR: 0.58; 95% CI: 0.25–1.37; one-sided p = 0.107). All adverse events associated with the MSKD were grade 1 or 2. There were no significant differences between the groups regarding the incidence of chemotherapy-related adverse events of grade ≥3. Patients undergoing MSKD treatment showed no decline in quality of life, and their microbiome exhibited significant enrichment of various beneficial bacterial taxa (p < .05; log-fold change ≥ 2).
Conclusion: The MSKD regimen is feasible in patients with pancreatic ductal adenocarcinoma. Although the sample size of this study was insufficient to draw definitive conclusions regarding clinical endpoints, the data suggest a trend toward improved progression-free survival and overall survival when MSKD is combined with gemcitabine, nab-paclitaxel, and cisplatin, without incurring additional toxicity or compromising patients’ quality of life. Larger-scale studies are warranted to further validate these findings.
参考文献 Reference
Jameson GS et al. Cancer 2026 ;132 :1124
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术后帕博利珠单抗联合belzutifan 用于透明细胞肾细胞癌 (4/11/2026)
Adjuvant pembrolizumab plus belzutifan for clear cell renal cell carcinoma: LITESPARK-022 study
这是一项 III 期, 双盲临床试验（LITESPARK-022, NCT05239728），该研究旨在评估帕博利珠单抗联合belzutifan 对比帕博利珠单抗联合安慰剂，用于接受肾切除术后复发风险增加的ccRCC患者的疗效与安全性。
方法：入组患者须符合以下条件：确诊为 M0期透明细胞肾细胞癌，且在接受肾切除术后具有中高危（pT2 Gr 4或肉瘤样变，或pT3任何分级，N0）或高危（pT4任何分级，N0；或任何pT和分级，N+）复发风险；或者确诊为M1期透明细胞肾细胞癌，但在接受手术治疗后已达到“无疾病证据”（M1 NED）状态。患者按1:1的比例随机分组，接受9个周期的静脉注射帕博利珠单抗（400 mg，每6周一次，疗程约1年），并联合口服 belzutifan（120 mg，每日一次）或安慰剂。主要终点是由研究者评估的无病生存期。次要终点包括总生存期（关键次要终点）及安全性。本文报告的是首次中期分析的结果。
结果：总体而言，共有1,841例患者被随机分组（其中921例分至帕博利珠单抗联合 belzutifan 组，920例分至帕博利珠单抗联合安慰剂组）。截至2025年8月23日，中位随访时间为28.4个月（范围：15.0–40.1个月）。与帕博利珠单抗联合安慰剂组相比，帕博利珠单抗联合belzutifan 组显著改善了无病生存期（HR 0.72；95% CI 0.59–0.87；P = 0.0003）。两组的中位无病生存期均尚未达到；估算的 24 个月无病生存率分别为 80.7%（95% CI 77.7–83.2）和 73.7%（95% CI 70.6–76.6）。在首次中期分析时，总生存期数据尚不成熟，共发生 87 例总生存期事件（帕博利珠单抗联合belzutifan 组 38 例，帕博利珠单抗联合安慰剂组 49 例）；在达到最终总生存期分析所需事件数的 29% 时，总生存期结果未达到统计学显著性（HR 0.78；95% CI 0.51–1.19；P = 0.1220）。帕博利珠单抗联合 belzutifan 组和帕博利珠单抗联合安慰剂组中，分别有 70% 和 71% 的患者完成了既定治疗。
在接受治疗的患者中，帕博利珠单抗联合belzutifan组有 52.1% 的患者发生了 ≥3 级的治疗期间出现的不良事件，而帕博利珠单抗联合安慰剂组的发生率为 30.2%；最常见的不良事件包括贫血（12.1% vs 0.4%）、丙氨酸转氨酶（ALT）升高（6.4% vs 2.0%）和低氧血症（4.6% vs 0%）。两组间 5 级不良事件（分别为 1.1% vs 1.2%）及治疗相关不良事件（分别为 0.3% vs 0.3%）的发生率相似。未观察到新的安全性信号。
结论：对于肾切除术后复发风险较高的透明细胞肾细胞癌患者，辅助帕博利珠单抗联合belzutifan治疗在无病生存期方面显示出具有统计学显著性和临床意义的改善，优于帕博利珠单抗联合安慰剂治疗；其安全性特征与各单药已知的安全性特征一致。这些结果支持将辅助帕博利珠单抗联合belzutifan治疗作为复发风险较高的肾细胞癌的一种潜在新 标准治疗方案。
This is a phase III, double-blind clinical trial (LITESPARK-022, NCT05239728) designed to evaluate the efficacy and safety of pembrolizumab in combination with belzutifan versus pembrolizumab in combination with placebo in patients with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence following nephrectomy.
Methods: Eligible patients were required to meet the following criteria: a confirmed diagnosis of M0 clear cell renal cell carcinoma with an intermediate-to-high risk (pT2 Gr 4 or sarcomatoid features; or pT3 any grade, N0) or high risk (pT4 any grade, N0; or any pT and grade, N+) of recurrence following nephrectomy; or a confirmed diagnosis of M1 clear cell renal cell carcinoma who had achieved a status of “no evidence of disease” (M1 NED) following surgical treatment. Patients were randomized in a 1:1 ratio to receive 9 cycles of intravenous pembrolizumab (400 mg every 6 weeks, for a duration of approximately 1 year) in combination with either oral belzutifan (120 mg once daily) or placebo. The primary endpoint was investigator-assessed disease-free survival (DFS). Secondary endpoints included overall survival (a key secondary endpoint) and safety. This report presents the results of the first interim analysis.
Results: Overall, a total of 1,841 patients were randomized (921 to the pembrolizumab-plus-belzutifan arm and 920 to the pembrolizumab-plus-placebo arm). As of August 23, 2025, the median follow-up duration was 28.4 months (range: 15.0–40.1 months). Compared with the pembrolizumab-plus-placebo arm, the pembrolizumab-plus-belzutifan arm demonstrated a significant improvement in DFS (HR 0.72; 95% CI 0.59–0.87; P = 0.0003). The median DFS has not yet been reached in either group; the estimated 24-month DFS rates were 80.7% (95% CI, 77.7–83.2) and 73.7% (95% CI, 70.6–76.6), respectively. At the time of the first interim analysis, overall survival (OS) data were immature, with a total of 87 OS events reported (38 in the pembrolizumab-plus-belzutifan group and 49 in the pembrolizumab-plus-placebo group); with 29% of the events required for the final OS analysis having occurred, the OS results did not reach statistical significance (HR, 0.78; 95% CI, 0.51–1.19; P = 0.1220). In the pembrolizumab-plus-belzutifan and pembrolizumab-plus-placebo groups, 70% and 71% of patients, respectively, completed the planned treatment.
Among treated patients, 52.1% in the pembrolizumab-plus-belzutifan group experienced treatment-emergent adverse events (TEAEs) of Grade ≥3, compared with 30.2% in the pembrolizumab-plus-placebo group; the most common adverse events included anemia (12.1% vs 0.4%), increased alanine aminotransferase (ALT) levels (6.4% vs 2.0%), and hypoxemia (4.6% vs 0%). The rates of Grade 5 adverse events (1.1% vs 1.2%) and treatment-related adverse events (0.3% vs 0.3%) were similar between the two groups. No new safety signals were observed.
Conclusion: For patients with clear cell renal cell carcinoma at high risk of recurrence following nephrectomy, adjuvant pembrolizumab combined with belzutifan demonstrated statistically significant and clinically meaningful improvements in disease-free survival, outperforming pembrolizumab combined with placebo; its safety profile was consistent with the known safety profiles of the individual agents. These results support the potential adoption of adjuvant pembrolizumab combined with belzutifan as a new standard of care for renal cell carcinoma at high risk of recurrence.
参考文献 Reference
Choueiri TK et al. J Clin Onc 2026 ; 44 [7, suppl Abstr LBA418]
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超低剂量免疫疗法治疗难治性实体瘤 (4/5/2026)
Ultra-low-dose immunotherapy in refractory solid tumors: DELII trial
方法: 在这项III期优效性随机试验中，患有晚期实体瘤且在接受过≥1线既往全身治疗后病情仍发生进展的患者，按1:1的比例随机分配至超低剂量纳武利尤单抗组（20 mg，每2周静脉滴注一次）或标准化疗组（根据肿瘤类型给予多西他赛或紫杉醇）。治疗持续至病情进展或出现不可耐受的毒性反应为止。主要终点指标为总生存期。
结果: 从2020年6月至2024年2月，共入组了500例患者, 两组各250例；其中52%的患者患有头颈部肿瘤，36%患有肺癌。既往治疗的中位线数为1线（范围：1-8线）；29%的患者曾接受过≥2线的既往治疗。超低剂量纳武利尤单抗组的中位生存期显著长于对照组：分别为5.88个月（95% CI：4.99-7.13）和4.70个月（95% CI：3.91-5.65；风险比 [HR] = 0.80 [95% CI：0.66-0.97]；P = 0.022）。两组的1年生存期率分别为27.3%和16.9%。两组的中位无进展生存期相似：超低剂量纳武利尤单抗组为2.04个月（95% CI：2.00-2.10），化疗组为2.09个月（95% CI：2.04-2.17）（HR = 1.03 [95% CI：0.86-1.23]；P = 0.77）。
使用超低剂量纳武利尤单抗时，≥3级治疗相关不良事件的发生率较低（42.5% 对 60.8%；P < .001）。超低剂量纳武利尤单抗组的生存质量显著优于对照组。
结论: 在既往接受过治疗的实体瘤患者中，超低剂量纳武利尤单抗相较于化疗，能显著改善总生存期，且伴随更少的严重毒性反应及更好的生存质量。
Methods: In this phase III randomized superiority trial, patients with advanced solid tumors whose disease had progressed following at least one line of prior systemic therapy were randomized in a 1:1 ratio to receive either ultra-low-dose nivolumab (20 mg administered intravenously every 2 weeks) or standard chemotherapy (docetaxel or paclitaxel, depending on tumor type). Treatment continued until disease progression or the occurrence of intolerable toxicity. The primary endpoint was overall survival.
Results: From June 2020 to February 2024, a total of 500 patients were enrolled, with 250 patients in each group; among them, 52% had head and neck tumors and 36% had lung cancer. The median number of prior lines of therapy was 1 (range: 1–8); 29% of patients had received at least two lines of prior therapy. Median overall survival was significantly longer in the ultra-low-dose nivolumab group compared to the control group: 5.88 months (95% CI: 4.99–7.13) versus 4.70 months (95% CI: 3.91–5.65; hazard ratio [HR] = 0.80 [95% CI: 0.66–0.97]; P = 0.022). The 1-year overall survival rates for the two groups were 27.3% and 16.9%, respectively. Median progression-free survival was similar in both groups: 2.04 months (95% CI: 2.00–2.10) in the ultra-low-dose nivolumab group versus 2.09 months (95% CI: 2.04–2.17) in the chemotherapy group (HR = 1.03 [95% CI: 0.86–1.23]; P = 0.77).
The incidence of grade ≥3 treatment-related adverse events was lower with ultra-low-dose nivolumab (42.5% vs. 60.8%; P < .001). Quality of life in the ultra-low-dose nivolumab group was significantly superior to that in the control group.
Conclusion: In patients with previously treated solid tumors, ultra-low-dose nivolumab significantly improved overall survival compared to chemotherapy, while being associated with fewer severe toxicities and better quality of life.
参考文献 Reference
Noronha V et al. J Clinc Onc 2026 : DOI: 10.1200/JCO-25-0154
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阿替利珠单抗联合 FOLFOX 治疗 III 期错配修复缺陷型结肠癌 (4/4/2026)
Atezolizumab plus FOLFOX for stage III dMMR colon cancer
方法: 在一项 III 期临床试验中，以 1:1 的比例将接受了肿瘤切除术的 III 期 dMMR 结肠癌患者随机分组：一组接受阿替利珠单抗联合 mFOLFOX6 辅助治疗 6 个月（随后继续单用阿替利珠单抗治疗，总疗程共 12 个月）；另一组仅接受 mFOLFOX6 治疗 6 个月。主要终点指标为无病生存期。次要终点指标包括总生存期及不良事件概况。
结果: 共有 355 例患者被分配至阿替利珠单抗联合 mFOLFOX6 治疗组，357 例患者被分配至 mFOLFOX6 单药治疗组。患者的中位年龄为 64 岁，其中 55.1% 为女性；53.9% 的患者肿瘤分期属于 T4, N2 或两者兼有（提示为高危病例）。在中位随访时间为 40.9 个月时，阿替利珠单抗联合 mFOLFOX6 组的 3 年无病生存率为 86.3%（95% 置信区间 [CI]：81.8% 至 89.8%），而 mFOLFOX6 单药组的 3 年无病生存率为 76.2%（95% CI：70.9% 至 80.6%）；两组间疾病复发或死亡的风险比（HR）为 0.50（95% CI：0.35 至 0.73；P < 0.001）。
在接受阿替利珠单抗联合 mFOLFOX6 治疗的患者中，84.1% 发生了 3 级或 4 级不良事件；而在仅接受 mFOLFOX6 治疗的患者中，这一比例为 71.9%。
结论: 在 mFOLFOX6 方案中加入阿替利珠单抗，显著改善了 III 期 dMMR 结肠癌患者的无病生存期。
Methods: In a phase III clinical trial, patients with stage III dMMR colon cancer who had undergone tumor resection were randomized in a 1:1 ratio: one group received 6 months of adjuvant therapy with atezolizumab combined with mFOLFOX6 (followed by continued atezolizumab monotherapy, for a total treatment duration of 12 months); the other group received mFOLFOX6 alone for 6 months. The primary endpoint was disease-free survival. Secondary endpoints included overall survival and the adverse event profile.
Results: A total of 355 patients were assigned to the atezolizumab-plus-mFOLFOX6 group, and 357 patients were assigned to the mFOLFOX6 monotherapy group. The median age of the patients was 64 years, and 55.1% were female; 53.9% of the patients had tumors staged as T4, N2, or both (indicating high-risk cases). At a median follow-up of 40.9 months, the 3-year disease-free survival rate was 86.3% (95% confidence interval [CI]: 81.8% to 89.8%) in the atezolizumab-plus-mFOLFOX6 group, compared with 76.2% (95% CI: 70.9% to 80.6%) in the mFOLFOX6 monotherapy group; the hazard ratio (HR) for disease recurrence or death between the two groups was 0.50 (95% CI: 0.35 to 0.73; P < 0.001).
Among patients treated with atezolizumab plus mFOLFOX6, 84.1% experienced grade 3 or 4 adverse events; in patients treated with mFOLFOX6 alone, this proportion was 71.9%.
Conclusions: The addition of atezolizumab to the mFOLFOX6 regimen significantly improved disease-free survival in patients with stage III dMMR colon cancer.
参考文献 Reference
Sinicrope FA et al. N Engl J Med 2026 ;394 :1156
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Odronextamab 联合CHOP 用于初治弥漫大B细胞淋巴瘤 (3/29/2026)
Odronextamab plus CHOP in untreated DLBCL: First results of OLYMPIA-3
Odronextamab 是一种基于人源 IgG4 的 CD20 × CD3 双特异性抗体，能够同时结合 T 细胞与恶性 B 细胞，从而介使T 细胞介导的细胞毒性作用。
这项开放标签研究分为两个部分进行设计。在第一部分中，研究人员对 Odronextamab 的剂量进行了递增和优化。在为期 21 天的治疗周期第 1 天给予标准的 CHOP 方案；Odronextamab 的给药始于第 8 天，最初采用 0.7/4/20 mg 的阶梯式递增剂量，随后按不同的剂量水平进行给药，频率先为每周一次，之后改为每两周一次。目前已报告了针对 80 mg 和 160 mg 剂量组的数据，这两个剂量组均采用每周给药方案，共计完成六个治疗周期。
研究的第二部分将继续采用 CHOP 方案，患者将被随机分配接受 Odronextamab（Odro-CHOP 方案）或利妥昔单抗（R-CHOP 方案）治疗。 该研究将 9 名既往未接受过治疗的患者分配至 80 mg 剂量组，将 13 名患者分配至 160 mg 剂量组。在第一部分的全部受试患者中，所有患者均患有伴有高危特征的新发弥漫大 B 细胞淋巴瘤。患者的中位年龄为 66 岁，其中 32% 的患者年龄在 75 岁及以上。原发细胞类型主要为非生发中心 B 细胞型（59%）。国际预后指数（IPI）评分为 3 分的患者占 36%，评分为 4-5 分的患者占 27%；95% 的患者处于 Lugano 分期 III-IV 期。
在 OLYMPIA-3 研究的第一部分（Part IA）中，接受 160 mg 剂量治疗的患者达到了 100% 的完全响应率 (78% 相对于80毫克剂量)。 所获得的完全响应具有持久性；目前尚未达到完全响应的中位持续时间及中位无进展生存期。
该项不含利妥昔单抗的治疗方案具有良好的安全性特征，因不良事件导致治疗中断的病例极少，且大多数患者均顺利完成了全部六个周期的治疗。
截至本次数据分析时，在 80 mg 剂量组入组的 9 名患者中，有 7 名（77.8%）已完成了第 1 至第 6 个治疗周期；其余 2 名患者因临床需要（经医生决定）提前终止了治疗。在160 mg剂量组中，全部13例患者均完成了第一周期治疗，84.6%的患者完成了第六周期治疗，另有2例患者因医生决定而提前终止了治疗。
所有接受 80 mg 和 160 mg 剂量 Odronextamab 治疗的患者均发生了 ≥ 3 级的治疗期间出现的不良事件。其中，导致治疗中断或延误的不良事件发生率分别为 66.7% 和 84.6%。未记录到剂量限制性毒性事件。 在上述两种剂量组中，最常见的治疗相关不良事件包括中性粒细胞减少症（77.3%）、细胞因子释放综合征（CRS，54.5%）和贫血（45.5%）。所有中性粒细胞减少症病例均为 3 级或 4 级；贫血病例中，也有半数达到了 3 级或 4 级。血小板减少症发生于 22.7% 的患者中，且几乎均为 3 级或 4 级。 相比之下，CRS 病例的严重程度仅限于 1 级（40.9%）或 2 级（13.6%）。为管理 CRS，27.3% 的患者接受了托珠单抗治疗，18.2% 的患者接受了类固醇治疗。CRS 主要发生于剂量递增阶段的最低剂量给药期，中位起病时间为 9 小时，中位持续时间为 3.8 个月。未发生免疫效应细胞相关神经毒性综合征或肿瘤溶解综合征的病例。 在接受上述两种剂量治疗的患者中，81.8% 发生了感染。其中，31.8% 为 3 级感染，9.1% 为 4 级感染。50% 的患者被诊断出患有机会性感染，其中仅一例为 ≥ 3 级；最常见的机会性感染包括巨细胞病毒再激活或再感染、COVID-19 以及口腔念珠菌病。
Odronextamab is a human IgG4-based CD20 × CD3 bispecific antibody capable of simultaneously binding to T cells and malignant B cells, thereby mediating T cell-mediated cytotoxicity. This open-label study was designed to be conducted in two parts. In the first part, researchers performed dose escalation and optimization for Odronextamab. The standard CHOP regimen was administered on Day 1 of each 21-day cycle; Odronextamab administration began on Day 8, initially utilizing a step-up dosing schedule of 0.7/4/20 mg, followed by administration at various dose levels—initially on a weekly basis, and subsequently every two weeks. Data have currently been reported for the 80 mg and 160 mg dose cohorts; both cohorts utilized a weekly dosing schedule for a total of six treatment cycles.
The second part of the study will continue to employ the CHOP regimen, wherein patients will be randomized to receive either Odronextamab (Odro-CHOP regimen) or rituximab (R-CHOP regimen). In the first part of the study, 9 previously untreated patients were assigned to the 80 mg dose cohort, and 13 patients were assigned to the 160 mg dose cohort. Among all subjects enrolled in the first part, every patient presented with newly diagnosed diffuse large B-cell lymphoma (DLBCL) accompanied by high-risk features. The median age of the patients was 66 years, with 32% of patients aged 75 years or older. The primary cell-of-origin subtype was non-germinal center B-cell (59%). Patients with an International Prognostic Index (IPI) score of 3 accounted for 36% of the cohort, while those with a score of 4–5 accounted for 27%; 95% of patients were classified as Lugano Stage III–IV.
In Part IA of the OLYMPIA-3 study, patients treated with the 160 mg dose achieved a 100% complete response rate (vs. 78% in 80 mg dose). The complete responses achieved were durable; the median duration of complete response and median progression-free survival have not yet been reached. This rituximab-free treatment regimen demonstrated a favorable safety profile, with very few cases of treatment discontinuation due to adverse events, and the majority of patients successfully completed all six cycles of treatment. As of the time of this data analysis, among the 9 patients enrolled in the 80 mg dose group, 7 (77.8%) had completed treatment cycles 1 through 6; the remaining 2 patients discontinued treatment early due to clinical necessity (per physician decision). In the 160 mg dose group, all 13 patients completed the first treatment cycle, and 84.6% completed the sixth cycle; another 2 patients discontinued treatment early per physician decision. All patients treated with Odronextamab at the 80 mg and 160 mg dose levels experienced treatment-emergent adverse events of grade ≥ 3. Among these, the incidence of adverse events leading to treatment interruption or delay was 66.7% and 84.6%, respectively. No dose-limiting toxicities were recorded. In both dose groups, the most common treatment-related adverse events included neutropenia (77.3%), cytokine release syndrome (CRS; 54.5%), and anemia (45.5%). All cases of neutropenia were grade 3 or 4; among cases of anemia, half were also grade 3 or 4. Thrombocytopenia occurred in 22.7% of patients, with nearly all cases being grade 3 or 4. In contrast, the severity of CRS cases was limited to grade 1 (40.9%) or grade 2 (13.6%). To manage CRS, 27.3% of patients received tocilizumab, and 18.2% received corticosteroids. CRS primarily occurred during the lowest-dose administration period of the dose-escalation phase; the median time to onset was 9 hours, and the median duration was 3.8 months. No cases of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or Tumor Lysis Syndrome (TLS) were observed. Among patients treated with the aforementioned two doses, 81.8% experienced infections. Of these, 31.8% were grade 3 infections, and 9.1% were grade 4 infections. 50% of patients were diagnosed with opportunistic infections, only one of which was Grade ≥ 3; the most common opportunistic infections included cytomegalovirus (CMV) reactivation or reinfection, COVID-19, and oral candidiasis.
参考文献 Reference
Michot J-M.ASH 2025 Ann Meeting abstr 65
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FDA 批准 Relacorilant 联合纳米炭紫杉醇用于治疗多种铂耐药性妇科肿瘤 (3/28/2026)
Relacorilant with nab-paclitaxel approved for several platinum-resistant gynecologic cancers
2026年3月25日，FDA批准了 Relacorilant（一种糖皮质激素受体拮抗剂）联合纳米炭紫杉醇（nab-paclitaxel），用于治疗已接受过 1 至 3 种既往全身治疗方案（其中至少一种包含贝伐珠单抗）的铂耐药性上皮性卵巢癌, 输卵管癌或原发性腹膜癌患者。这是一项多中心, 开放标签试验（ROSELLA, NCT05257408），共纳入了 381 名患有铂耐药性上皮性卵巢癌, 输卵管癌或原发性腹膜癌的患者。入组患者允许接受最多 3 种既往全身治疗方案，且必须曾接受过贝伐珠单抗治疗。该试验排除了需要长期或频繁使用糖皮质激素的患者。患者被随机分组（按 1:1 的比例），分别接受 Relacorilant 联合纳米炭紫杉醇治疗，或仅接受纳米炭紫杉醇单药治疗。 主要疗效终点指标包括：由盲法独立中心审阅委员会依据 RECIST 1.1 版标准评估的无进展生存期，以及总生存期。在 Relacorilant 联合纳米炭紫杉醇治疗组中，中位无进展生存期为 6.5 个月（95% CI：5.6, 7.4）；而在纳米炭紫杉醇单药治疗组中，中位无进展生存期为 5.5 个月（95% CI：3.9, 5.9）（风险比 [Hazard ratio] 为 0.70 [95% CI：0.54, 0.91]；双侧 p 值 = 0.0076）。在 Relacorilant 联合纳米炭紫杉醇治疗组中，中位总生存期为 16 个月（95% CI：13, 18.3）；在纳米炭紫杉醇单药治疗组中，中位总生存期为 11.9 个月（95% CI：10, 13.8）（风险比 [Hazard ratio] 0.65 [95% CI：0.51, 0.83]；双侧 p 值 0.0004）。
处方信息中包含一项禁忌症：对于因挽救生命指征而需使用皮质类固醇治疗的患者，禁止使用本药。此外，处方信息还列出了针对中性粒细胞减少症和严重感染, 肾上腺功能不全, 经糖皮质激素治疗的疾病病情加重，以及胚胎-胎儿毒性的警告与注意事项。在接受 Relacorilant 联合纳米炭紫杉醇治疗的患者中，最常见的不良反应（发生率 ≥ 20%）, 包括实验室检查异常, 主要有血红蛋白降低、中性粒细胞减少, 疲乏, 恶心, 腹泻, 血小板减少, 皮疹和食欲下降。
Relacorilant 的推荐剂量为 150 mg，口服给药；给药时间为每次纳米炭紫杉醇输注的前一天, 当天及后一天，直至疾病进展或出现不可耐受的毒性。纳米炭紫杉醇的推荐剂量为 80 mg/m²，通过静脉输注给药；给药时间为每 28 天为一个周期的第 1 天、第 8 天和第 15 天，直至疾病进展或出现不可耐受的毒性。
On March 25, 2026, the FDA approved Relacorilant—a glucocorticoid receptor antagonist—in combination with nab-paclitaxel for the treatment of patients with platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have received 1 to 3 prior lines of systemic therapy, at least one of which included bevacizumab. This approval was based on a multicenter, open-label trial (ROSELLA, NCT05257408) that enrolled a total of 381 patients with platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Enrolled patients were permitted to have received up to 3 prior lines of systemic therapy and were required to have previously received bevacizumab. The trial excluded patients requiring chronic or frequent use of glucocorticoids. Patients were randomized (in a 1:1 ratio) to receive either Relacorilant in combination with nab-paclitaxel or nab-paclitaxel monotherapy. The primary efficacy endpoints included progression-free survival (PFS), as assessed by a blinded independent central review committee according to RECIST version 1.1 criteria, and overall survival (OS).
In the Relacorilant plus nab-paclitaxel arm, the median PFS was 6.5 months (95% CI: 5.6, 7.4); in the nab-paclitaxel monotherapy arm, the median PFS was 5.5 months (95% CI: 3.9, 5.9) (Hazard Ratio [HR] = 0.70 [95% CI: 0.54, 0.91]; two-sided p-value = 0.0076). In the Relacorilant plus nab-paclitaxel treatment arm, the median overall survival was 16 months (95% CI: 13, 18.3); in the nab-paclitaxel monotherapy arm, the median overall survival was 11.9 months (95% CI: 10, 13.8) (Hazard Ratio 0.65 [95% CI: 0.51, 0.83]; two-sided p-value 0.0004).
The prescribing information includes one contraindication: this drug is contraindicated in patients requiring corticosteroid treatment for life-saving indications. Furthermore, the prescribing information lists warnings and precautions regarding neutropenia and severe infections, adrenal insufficiency, worsening of conditions treated with glucocorticoids, and embryo-fetal toxicity. Among patients receiving Relacorilant in combination with nab-paclitaxel, the most common adverse reactions (incidence ≥ 20%)—including laboratory abnormalities—were decreased hemoglobin, neutropenia, fatigue, nausea, diarrhea, thrombocytopenia, rash, and decreased appetite.
The recommended dose of Relacorilant is 150 mg, administered orally, on the day before, the day of, and the day after each nab-paclitaxel infusion, until disease progression or unacceptable toxicity occurs. The recommended dose of nab-paclitaxel is 80 mg/m², administered via intravenous infusion, on Days 1, 8, and 15 of a 28-day cycle, until disease progression or unacceptable toxicity occurs.
参考文献 Reference
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Tucatinib 联合 Trastuzumab 和 Pertuzumab 对比安慰剂作为 HER2 阳性转移性乳腺癌一线维持治疗 (3/22/2026)
Tucatinib versus placebo in combination ith trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer: HER2CLIMB-05
方法: 这是一项III期临床试验 （HER2CLIMB-05, NCT05132582）, 入组患者均为经中心实验室确诊的HER2 阳性转移性乳腺癌患者，且在完成诱导治疗后无疾病进展证据，同时无脑转移或仅有无症状脑转移。患者按 1:1 的比例随机分配至 Tucatinib 组（300 mg，每日两次）或安慰剂组，两组均联合使用 Trastuzumab/Pertuzumab 进行治疗。主要终点是由研究者评估的c；次要终点包括总生存期, 经盲法独立中心评估的无进展生存期, 中枢神经系统无进展生存期以及安全性。
结果: 在 2022 年 3 月至 2024 年 7 月期间，共有 654 名患者被随机分配至 Tucatinib 组（n = 326）和安慰剂组（n = 328）。所有入组患者均为女性（中位年龄 54 岁）；其中 69.3% 为初诊即转移性乳腺癌（de novo MBC），52.6% 为激素受体阳性，12.4% 在基线时存在脑转移或有脑转移病史。在此次主要分析中，与安慰剂组相比，加用 Tucatinib 显著改善了无进展生存期（风险比 [HR]：0.641 [95% CI：0.514–0.799]；P < 0.0001；中位无进展生存期：24.9 个月 对比 16.3 个月）；无论患者是否存在脑转移或激素受体状态如何，均观察到了无进展生存期获益。总生存期数据目前尚不成熟。
在 Tucatinib 组中，最常见的治疗期间出现的不良事件包括腹泻（72.7%）, 恶心（33.1%）以及肝酶升高（ALT： 28.2%；AST：25.8%）；其中，上述不良事件达到 ≥3 级的比例分别为 6.1%、0.9%、13.5% 和 7.1%。在该组中，有 13.5% 的患者因不良事件而停用 Tucatinib。
结论: 在曲妥珠单抗和帕妥珠单抗治疗方案中加用 Tucatinib，显示出无进展生存期的改善，且未发现新的安全性信号；这有望成为 HER2 阳性转移性乳腺癌患者一线维持治疗的一种选择。
Methods: This is a phase III clinical trial (HER2CLIMB-05, NCT05132582) that enrolled patients with centrally confirmed HER2-positive metastatic breast cancer who demonstrated no evidence of disease progression following induction therapy and who had either no brain metastases or only asymptomatic brain metastases. Patients were randomized in a 1:1 ratio to receive either tucatinib (300 mg twice daily) or placebo; both groups received treatment in combination with trastuzumab and pertuzumab. The primary endpoint was investigator-assessed progression-free survival (PFS); secondary endpoints included overall survival (OS), blinded independent central review-assessed PFS, central nervous system PFS, and safety.
Results: Between March 2022 and July 2024, a total of 654 patients were randomized to the tucatinib group (n = 326) or the placebo group (n = 328). All enrolled patients were female (median age: 54 years); 69.3% presented with de novo metastatic breast cancer, 52.6% were hormone receptor-positive, and 12.4% had brain metastases or a history of brain metastases at baseline. In this primary analysis, the addition of tucatinib significantly improved PFS compared to placebo (Hazard Ratio [HR]: 0.641 [95% CI: 0.514–0.799]; P < 0.0001; median PFS: 24.9 months vs. 16.3 months); PFS benefits were observed regardless of the presence of brain metastases or hormone receptor status. Overall survival data remain immature at this time.
In the Tucatinib group, the most common treatment-emergent adverse events included diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%); among these, the rates of grade ≥3 events were 6.1%, 0.9%, 13.5%, and 7.1%, respectively. In this group, 13.5% of patients discontinued Tucatinib due to adverse events.
Conclusion: The addition of Tucatinib to a treatment regimen of trastuzumab and pertuzumab demonstrated an improvement in PFS and revealed no new safety signals. This holds promise as an option for first-line maintenance therapy in patients with HER2-positive metastatic breast cancer.
参考文献 Reference
Dieras V et al. J Clin Onc 2025 ; DOJ: 10.1200/JCO-25-02600
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首项 I 期试验针对多发性骨髓瘤的体内 CAR T 细胞疗法 (3/21/2026)
First phase I human study of in vivo CAR T in myeloma
通过静脉注射一种慢病毒载体, KLB-1010，在体内诱导生成全人源抗B 细胞成熟抗原（BCMA） CAR-T 细胞。这与当前将 T 细胞取出并在实验室进行体外制备的模式不同, 消除了进行预处理性淋巴清除的必要，也简化了当前 CAR-T 细胞疗法在实施过程中所涉及的物流环节并降低了成本和时间。 临床前研究显示，与体外制备的 CAR-T 细胞相比，该疗法展现出了更为优越的抗骨髓瘤活性；该疗法还能诱导生成分化程度较低, 呈记忆样表型的 T 细胞群体，而这类细胞表型通常与 CAR-T 细胞在体内的持久存活能力增强以及肿瘤清除效果提升相关。
该试验招募的受试者均为复发性或难治性 多发性骨髓瘤患者，且此前均已接受过免疫调节剂, 蛋白酶体抑制剂以及抗 CD38 抗体的治疗，但尚未接受过针对 BCMA 的靶向治疗。 inMMyCAR 研究计划招募 20 名受试者。首批 4 名已接受治疗受试者均属于具有高危细胞遗传学特征的病例。在这 4 名患者中，有 3 名接受了 2×10^7 IU/kg 剂量（剂量水平 1）的治疗，另有 1 名接受了 6×10^6 IU/kg 剂量（剂量水平 –1）的治疗。之所以对治疗剂量进行下调，是因为研究人员在治疗过程中观察到了极高的疗效以及良好的安全性特征。 尽管未进行淋巴清除预处理，患者体内的 CAR-T 细胞依然实现了有效的扩增。在第15天进行的血液检测中，检测到了CAR阳性T细胞，其水平占CD3阳性T细胞总数的22%至85%，且其中包含不同比例的CD4和CD8细胞。值得注意的是，最高水平（85%）出现在–1剂量组的患者中。针对所有四名患者，KLN-1010均诱导产生了富含低分化T细胞及记忆型CAR T细胞的CAR-T细胞群。 在血液和骨髓中观察到的CAR-T细胞峰浓度（Cmax）及其长达3个月的体内存续时间，均与目前已上市的体外制备产品处于同一水平。其细胞扩增倍数（水平）达到了每微克DNA对应51,000至108,000个拷贝。 所有患者均在接受治疗后的1个月内实现了微小残留病（MRD）阴性：前三名患者在10⁻⁶的检测灵敏度下达到了MRD阴性标准；而第四名患者（即接受–1剂量组治疗的患者）在第1个月时，于10⁻⁵的检测灵敏度下达到了MRD阴性标准。截至第3个月的随访时点，仍有两名患者维持MRD阴性状态。 随访时间最长的一名患者（随访期约为5个月）依据国际骨髓瘤工作组（IMWG）的判定标准，实现了完全响应。其余患者均处于部分响应状态，这主要归因于其体内副蛋白清除过程的滞后。
在这四名受试患者中，未观察到任何免疫效应细胞相关神经毒性综合征（ICANS）的病例。共发生三例细胞因子释放综合征（CRS），且均为1级或2级。此外，报告了一例短暂性的4级中性粒细胞减少症，经判定该症状系由“边缘化”（margination）效应所致。此外，一名患者出现了3级贫血，另一名患者出现了1级血小板减少症。共有三名患者发生了输注反应，其中一例为3级事件；所有反应均通过标准处理措施迅速缓解。
Through intravenous administration of a lentiviral vector, KLB-1010, to induce the *in vivo* generation of fully human anti-B-cell maturation antigen (BCMA) CAR-T cells is a novel approach different from the current paradigm—which involves extracting T cells for *ex vivo* preparation in a laboratory setting—thereby eliminating the need for lymphodepleting pretreatment, simplifying the logistical complexities associated with current CAR-T cell therapies, and reducing both costs and turnaround times. Preclinical studies have demonstrated that, compared to *ex vivo*-generated CAR-T cells, this therapy exhibits superior anti-myeloma activity. Furthermore, the therapy induces the generation of a T-cell population characterized by a less differentiated, memory-like phenotype—a cellular profile typically associated with enhanced *in vivo* persistence and improved tumor clearance efficacy. The trial enrolled subjects with relapsed or refractory multiple myeloma who had previously received treatment with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies, but had not yet undergone BCMA-targeted therapy. The inMMyCAR study is designed to enroll a total of 20 subjects. The initial cohort of four treated subjects consisted entirely of patients presenting with high-risk cytogenetic features. Of these four patients, three received a dose of 2×10^7 IU/kg (Dose Level 1), while one received a dose of 6×10^6 IU/kg (Dose Level –1). The decision to de-escalate the treatment dose was prompted by the researchers’ observation of exceptionally high therapeutic efficacy coupled with a favorable safety profile during the course of treatment. Despite the absence of lymphodepleting pretreatment, effective in vivo expansion of CAR-T cells was successfully achieved in the patients. Blood analyses performed on Day 15 detected CAR-positive T cells at levels ranging from 22% to 85% of the total CD3-positive T-cell population, comprising varying proportions of CD4 and CD8 cells. Notably, the highest level (85%) was observed in the patient treated at Dose Level –1. In all four patients, KLN-1010 induced the generation of a CAR-T cell population enriched with less-differentiated T cells and memory-like CAR-T cells. The peak concentrations (Cmax) of CAR-T cells observed in the blood and bone marrow—along with their persistence in vivo for up to three months—were comparable to those of currently marketed ex vivo-manufactured products. The level of cellular expansion reached 51,000 to 108,000 copies per microgram of DNA. All patients achieved minimal residual disease (MRD) negativity within one month of treatment: the first three patients met the MRD-negative criteria at a detection sensitivity of 10⁻⁶, while the fourth patient (treated in the –1 dose cohort) achieved MRD negativity at a sensitivity of 10⁻⁵ at the one-month time point. As of the three-month follow-up, two patients maintained an MRD-negative status. The patient with the longest follow-up duration (approximately five months) achieved a complete response according to the International Myeloma Working Group (IMWG) criteria. The remaining patients were in a state of partial response, primarily attributed to a lag in the clearance of paraproteins in vivo.
Among these four treated patients, no cases of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were observed. A total of three cases of Cytokine Release Syndrome (CRS) occurred, all of which were grade 1 or 2. Additionally, one case of transient grade 4 neutropenia was reported, which was determined to be caused by a “margination” effect. Furthermore, one patient experienced grade 3 anemia, and another experienced grade 1 thrombocytopenia. A total of three patients experienced infusion reactions, one of which was a Grade 3 event; all reactions were rapidly resolved through standard management measures.
参考文献 Reference
Harrison J et al. 2025 ASH Ann Meeting & Exposition Abstr LBA-1
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消融术与手术治疗T1a期肾细胞癌的长期疗效相当 (3/15/2026)
Ablation and surgery for T1a renal cell carcinoma demonstrate comparable long-term outcomes: A Danish Nationwide Registry Study
目的: 比较T1a期肾细胞癌患者接受消融术, 手术切除和肾切除术的长期疗效。
方法: 这项回顾性全国性登记队列研究纳入了2013年1月至2021年12月期间在丹麦确诊为T1a期肾细胞癌的成年患者。患者接受了肿瘤消融术, 手术切除或肾切除术治疗。主要终点为疾病进展，定义为远处转移或局部复发。次要结局指标包括住院时长和治疗后30天内的医院就诊次数（不包括常规的定期随访）。采用竞争风险回归分析疾病进展，并报告风险比及其P值。其他组间比较采用χ²检验和Wilcoxon秩和检验。
结果: 共纳入1, 862例患者（中位年龄64岁[四分位间距55-71岁]；男性1,305例）。校正混杂因素后，消融组和切除组的疾病进展风险无显著差异（风险比1.46 [95% CI：0.60-3.56]；P = 0.40）。局部复发在消融术后最为常见（消融术：540例患者中有13例[2.41%]；切除术：1002例患者中有12例[1.20%]；肾切除术：320例患者中无复发[0%]；P = .007），但可通过后续手术治疗。远处转移在肾切除术后最为常见（消融术：540例患者中有9例[1.67%]；切除术：1002例患者中有19例[1.90%]；肾切除术：320例患者中有14例[4.38%]；P = .02）。消融术的住院时间最短（中位住院时间：消融术0天，切除术2天，肾切除术2天；P < .001）。消融术治疗后30天内住院次数最少（中位数：消融术1次[四分位距，0-2]，切除术1次[四分位距，1-2]，肾切除术1次[四分位距，1-2]；P = .001），提示消融术并发症更少。
结论: 对于T1a期肾细胞癌患者，消融术治疗的疾病进展风险与其他治疗方法相当，但并发症更少，住院时间更短。
Objective: To compare the long-term efficacy of ablation, surgical resection, and nephrectomy in patients with T1a renal cell carcinoma.
Methods: This retrospective national registry cohort study included adult patients diagnosed with T1a renal cell carcinoma in Denmark between January 2013 and December 2021. Patients underwent tumor ablation, surgical resection, or nephrectomy. The primary endpoint was disease progression, defined as distant metastasis or local recurrence. Secondary endpoints included length of hospital stay and number of hospital visits within 30 days post-treatment (excluding routine follow-up). Competitive hazard regression analysis was used to analyze disease progression, and hazard ratios and p-values were reported. Other intergroup comparisons were performed using the χ² test and Wilcoxon rank-sum test.
Results: A total of 1,862 patients were included (median age 64 years [interquartile range 55–71 years]; 1,305 were male). After adjusting for confounding factors, there was no significant difference in the risk of disease progression between the ablation and resection groups (hazard ratio 1.46 [95% CI: 0.60–3.56]; P = 0.40). Local recurrence was most common after ablation (ablation: 13 cases in 540 patients [2.41%]; resection: 12 cases in 1002 patients [1.20%]; nephrectomy: no recurrence in 320 patients [0%]; P = .007), but could be treated with subsequent surgery. Distant metastasis was most common after nephrectomy (ablation: 9 cases in 540 patients [1.67%]; resection: 19 cases in 1002 patients [1.90%]; nephrectomy: 14 cases in 320 patients [4.38%]; P = .02). Ablation resulted in the shortest hospital stay (median hospital stay: 0 days for ablation, 2 days for resection, and 2 days for nephrectomy; P < .001). The fewest hospitalizations within 30 days after ablation were also observed (median: 1 ablation [interquartile range, 0–2], 1 resection [interquartile range, 1–2], and 1 nephrectomy [interquartile range, 1–2]; P = .001), suggesting fewer complications with ablation.
Conclusion: For patients with T1a stage renal cell carcinoma, the risk of disease progression with ablation is comparable to other treatment methods, but with fewer complications and shorter hospital stays.
参考文献 Reference
Ahrenfeldt J et al. Radiology 2026;318: https://doi.org/10.1148/radiol.251485
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一种诊断治疗晚期胰腺导管腺癌的新型 KRAS G12D 抑制剂 (3/14/2026)
A novel KRAS G12D inhibitor for advanced pancreatic ductal adenocarcinoma
INCB161734 专门靶向 KRAS G12D 突变。这是一项 II 期临床试验，共有 61 名患者接受了 INCB161734 单药治疗；另有 44 名患者接受了该 KRAS 抑制剂与两种标准治疗化疗方案之一的联合治疗——即吉西他滨联合白蛋白结合型紫杉醇，或改良版 FOLFIRINOX 方案。在此之前，对 INCB161734 的多个剂量水平进行评估确定 1200 mg/天为推荐的 II 期临床试验剂量。参加者主要属于三线及以上治疗阶段的患者，其中绝大多数患者此前已接受过两线治疗。截至 2025 年 11 月的数据截止日期，仍有 69% 的患者在接受治疗。
推荐的 II 期试验剂量总体耐受性良好，因治疗相关不良事件而导致剂量中断或减量的病例极少，仅有两例因不良事件而终止治疗。在 16 例接受每日 1200 mg KRAS 抑制剂联合吉西他滨加白蛋白结合型紫杉醇治疗且可进行疗效评估的患者中，43.8% 的患者出现了导致该新型药物剂量中断的治疗相关不良事件，6.3% 的患者出现了导致剂量减量的不良事件；无患者因不良事件而终止该药物的治疗。化疗中断见于 37.5% 的患者，化疗剂量减量见于 43.8% 的患者；无患者因药物相关原因而终止化疗。主要毒性反应为中性粒细胞减少症，约 40% 的患者出现 3 级或更高级别的该不良事件。在 7 例接受每日 1200 mg INCB161734 联合改良版 FOLFIRINOX（mFOLFIRINOX）方案治疗且可进行疗效评估的患者中，有 3 例出现了导致治疗中断的治疗相关不良事件；无患者因不良事件而需要减量或终止治疗。不良事件导致 4 例患者化疗中断，4 例患者化疗减量，以及 2 例患者终止化疗。
INCB161734 在给药仅数周后便诱导产生了迅速的分子学应答；在那些血浆 ctDNA 中可检测到 KRAS G12D 变异的患者群体中（占总人群的 80%），接受 1200 mg 剂量治疗的患者中有三分之二实现了早期分子学应答（即变异等位基因频率降低了 90%）。该药物与化疗联用时，同样展现出了显著的分子学应答。INCB161734 单药疗法产生 37% 的客观响应率（主要是在接受三线以上治疗的患者中）, 对于联合治疗组来说，疗效信号还未成熟。
INCB161734 specifically targets the KRAS G12D mutation. This is a phase II clinical trial in which 61 patients received INCB161734 as monotherapy; an additional 44 patients received the KRAS inhibitor in combination with one of two standard-of-care chemotherapy regimens—gemcitabine plus nab-paclitaxel, or a modified version of FOLFIRINOX. Prior to this, evaluation of multiple dose levels of INCB161734 determined 1200 mg/day as the recommended phase II clinical trial dose. Many participants received third-line and above treatment, and the vast majority of patients have previously received two-line treatment. As of the data cutoff date of November 2025, 69% of patients were still receiving treatment. The recommended phase II trial doses were generally well tolerated, with minimal dose interruptions or reductions due to treatment-related adverse events and only two discontinuations due to adverse events. Among 16 patients who were evaluable for efficacy and were treated with 1200 mg daily of KRAS inhibitor plus gemcitabine and nab-paclitaxel, 43.8% experienced treatment-related adverse events that led to dose interruption of the novel agent, and 6.3% experienced adverse events that resulted in dose reduction; no patients discontinued treatment with the drug due to adverse events. Chemotherapy interruptions occurred in 37.5% of patients, and chemotherapy dose reductions occurred in 43.8% of patients; no patients discontinued chemotherapy for drug-related reasons. The main toxic effect was neutropenia, which was grade 3 or higher in approximately 40% of patients. Of the 7 patients evaluable for efficacy who received INCB161734 1200 mg daily in combination with modified FOLFIRINOX, 3 experienced treatment-related adverse events that led to treatment discontinuation; no patients required dose reduction or discontinuation of treatment due to adverse events. Adverse events resulted in discontinuation of chemotherapy in 4 patients, dose reduction in 4 patients, and discontinuation of chemotherapy in 2 patients.
INCB161734 induced a rapid molecular response just weeks after dosing; in a population of patients with detectable KRAS G12D variants in plasma ctDNA (80% of the population), two-thirds of patients treated with the 1200 mg dose achieved an early molecular response (i.e., a 90% reduction in variant allele frequency). The drug also demonstrated significant molecular responses when combined with chemotherapy. INCB161734 monotherapy produced an objective response rate of 37% (primarily in patients receiving more than three lines of therapy), while an efficacy signal is still not mature for the combination arm.
参考文献 Reference
Wainberg ZA et al. 2026 ASCO GI Cancers Symp Abstr 654
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ctDNA 指导肌层浸润性膀胱癌的疗效适应性膀胱保留治疗 (3/8/2026)
ctDNA to guide response-adapted bladder preservation in muscle invasive bladder cancer: RETAIN trials
背景：II 期 RETAIN 1 和 2 试验 (NCT04506554)评估了一种疗效适应性方法，用于识别接受新辅助治疗后可安全进行膀胱保留主动监测的肌层浸润性膀胱癌患者。RETAIN-1 评估了 AMVAC (化疗)方案，RETAIN-2 评估了纳武单抗联合 AMVAC 方案。本报告显示了RETAIN-2研究的最新结果，并整合了RETAIN-1/2研究中的ctDNA数据，以评估ctDNA在膀胱保留风险分层中的作用。
方法：RETAIN-2研究纳入了接受 AMVAC 联合纳武单抗治疗的 cT2-T3N0M0期肌层浸润性膀胱癌患者。对经尿道膀胱肿瘤切除术标本进行ATM, ERCC2 或 RB1基因突变测序。携带1个以上突变且临床完全响应（经复查经尿道膀胱检查, 尿细胞学和 CT 检查）的患者进入主动监测；其余患者接受膀胱靶向治疗。主要终点为意向治疗人群的2年无转移生存期。两项试验的血浆样本均在基线和治疗后使用 Signatera试剂盒进行分析；RETAIN-2研究还包括治疗后3个月和6个月的血浆样本采集。
结果：在 71 例可评估的 RETAIN-2 患者（中位年龄 68 岁；77% 为男性；42% 为 cT3 期）中，57 例（80.3%）在 29.2 个月的随访期内仍无转移。意向治疗人群的 2 年无转移生存率估计为 79.8%（95% CI 70–90%），主动监测人群的 2 年无转移生存率估计为 80%（95% CI 64–100%）。在 22 例主动监测患者中，8 例（36%）出现膀胱复发，4 例（18%）发生转移，其中 4 例需要挽救性膀胱切除术，3 例需要挽救性放化疗；16 例（73%）保持无转移状态且膀胱完整。在两项试验（RETAIN-1/2）中，共分析了来自 111 例患者的 274 个循环肿瘤 DNA (ctDNA) 时间点。基线和治疗后ctDNA阳性率分别为42.2%和13.6%。在基线阳性患者中，72.7%（32/44）的患者 ctDNA转阴。治疗后 ctDNA阴性或ctDNA转阴（由基线阳性转阴）的患者复发风险显著低于治疗后ctDNA阳性或未转阴的患者（复发率：阴性/转阴组分别为34.8%和43.8%，阳性/未转阴组分别为85.7%和91.7%；p < 0.001和p < 0.01）。在治疗后ctDNA阴性的主动监测患者中，12个月/24个月的无转移生存期分别为97.1%/82.4%，表明转移控制具有很强的预测价值。然而，12个月/24个月的无复发生存率分别为62.9%/50.7%，主要受局部复发的影响。在22例复发的主动监测患者中，19例在治疗后ctDNA检测呈阴性。仅有3例主动监测患者ctDNA检测呈阳性。
结论：RETAIN-2有望达到其2年无转移生存期的主要终点。虽然治疗后ctDNA阴性可以预测转移控制，但它并不能可靠地预测主动监测患者的局部复发。这一局限性可能反映了膀胱癌特有的场效应，或者仅仅是血浆ctDNA对检测局限于膀胱的微小残留病灶的敏感性较差。未来的膀胱保留治疗策略或许可以受益于将基于疗效的治疗选择与ctDNA和尿液肿瘤DNA的连续监测相结合。
Background: The phase II RETAIN 1 and 2 trials (NCT04506554) evaluated an efficacy-adaptive approach to identify patients with muscle-invasive bladder cancer who could safely undergo active surveillance with bladder preservation after neoadjuvant therapy. RETAIN-1 evaluated the AMVAC (chemotherapy) regimen, and RETAIN-2 evaluated nivolumab in combination with AMVAC. This report presents the latest results from the RETAIN-2 study that integrates ctDNA data from the RETAIN-1/2 studies to assess the role of ctDNA in bladder preservation risk stratification.
Methods: The RETAIN-2 study enrolled patients with cT2-T3N0M0 stage muscle-invasive bladder cancer who received AMVAC in combination with nivolumab. Specimens from transurethral bladder resection were sequenced for ATM, ERCC2, or RB1 gene mutations. Patients carrying one or more mutations and achieving complete clinical response (verified by repeat TUR examinations, urine cytology, and CT scans) were enrolled in active surveillance; the remaining patients received targeted bladder therapy. The primary endpoint was 2-year metastasis-free survival in the intention-to-treat population. Plasma samples from both trials were analyzed at baseline and post-treatment using the Signatera kit; the RETAIN-2 study also included plasma collection at 3 and 6 months post-treatment.
Results: Of the 71 evaluable RETAIN-2 patients (median age 68 years; 77% male; 42% cT3 stage), 57 (80.3%) remained metastasis-free during a 29.2-month follow-up period. The estimated 2-year metastasis-free survival rate was 79.8% (95% CI 70–90%) in the intention-to-treat population and 80% (95% CI 64–100%) in the active surveillance population. Of the 22 patients actively monitored, 8 (36%) experienced bladder recurrence, and 4 (18%) developed metastases, of which 4 required salvage cystectomy and 3 required salvage chemoradiotherapy; 16 (73%) remained metastatic-free and had intact bladders. In the two trials (RETAIN-1/2), a total of 274 circulating tumor DNA (ctDNA) time points from 111 patients were analyzed. The baseline and post-treatment ctDNA positivity rates were 42.2% and 13.6%, respectively. Among patients with baseline positivity, 72.7% (32/44) achieved ctDNA negativity. Patients who were ctDNA negative or ctDNA seroconversion (from baseline positive to negative) after treatment had a significantly lower risk of relapse than those who were ctDNA positive or not seroconverted after treatment (relapse rates: 34.8% and 43.8% in the negative/seroconversion group, respectively; 85.7% and 91.7% in the positive/not seroconversion group, respectively; p < 0.001 and p < 0.01). In active surveillance patients who were ctDNA negative after treatment, the 12-month/24-month metastasis-free survival was 97.1%/82.4%, indicating strong predictive value for metastasis control. However, the 12-month/24-month relapse-free survival was 62.9%/50.7%, mainly affected by local relapse. Of the 22 active surveillance patients with relapse, 19 were ctDNA negative after treatment. Only 3 active surveillance patients were ctDNA positive.
Conclusion: RETAIN-2 is expected to meet its primary endpoint of 2-year metastasis-free survival. While a negative ctDNA result after treatment can predict metastasis control, it cannot reliably predict local recurrence in patients under active surveillance. This limitation may reflect the field effect specific to bladder cancer, or it may simply be due to the poor sensitivity of plasma ctDNA in detecting minimal residual disease confined to the bladder. Future bladder-preserving treatment strategies may benefit from combining efficacy-based treatment selection with continuous monitoring of ctDNA and urinary tumor DNA.
参考文献 Reference
Ghatalia P. et al. J Clin Onc 2026; 44 [7, suppl Abstr LBA632]
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Cadonilimab治疗复发性宫颈癌 (3/7/2026)
Bispecific cadonilimab in recurrent cervical cancer
Cadonilimab 是一种首创的双特异性抗体，靶向PD-1和CTLA-4。这是一项II期临床试验 (COMPASSION-03, NCT03852251），该试验纳入了99例既往接受过含铂化疗后病情进展的复发或转移性宫颈癌患者。该试验中的患者每两周接受一次Cadonilimab静脉注射治疗。18% 的入组患者 PD-L1 联合阳性评分低于 1，36% 的患者曾接受过至少 2 线全身治疗。该试验的主要终点是发生不良事件和剂量限制性毒性的患者人数。中位随访时间为26.5个月。研究者根据最佳总体响应对结果进行分层，以量化治疗深度的影响。
结果: 在达到完全响应的患者中，中位总生存期和中位无进展生存期均尚未达到。完全响应患者的12个月无进展生存率为84.6%（P < 0.0001）。24个月总生存率为100.0%（P = 0.0002）。 达到部分响应的患者也显示出良好的预后，中位总生存期尚未达到，24个月总生存率为63%（P = 0.0002）。该组的中位无进展生存期为11.17个月，12个月无进展生存率为47.3%（P < 0.0001）。完全响应组和部分响应组的中位响应时间相似，分别为1.84个月和1.87个月。完全响应组的中位响应持续时间尚未达到。无论PD-L1表达状态如何，Cadonilimab单药治疗在总体人群中均获得了17.5个月的中位总生存期（95% CI，11.4个月至无法估计）；18个月和24个月的总生存率分别为47.8%和40.9%。
常见副作用包括： 疲劳, 恶心, 皮疹, 腹泻, 甲状腺功能减退, 贫血以及输液相关反应。3级不良事件，例如肺炎, 结肠炎或严重皮肤反应通常可控。
研究结果已在第27届欧洲妇科肿瘤学大会上发表。
Cadonilimab is a first-in-class bispecific antibody targeting PD-1 and CTLA-4. This was a phase II clinical trial (COMPASSION-03, NCT03852251) that enrolled 99 patients with recurrent or metastatic cervical cancer whose disease had progressed after prior platinum-based chemotherapy. Patients in this trial received intravenous cadonilimab every two weeks. Eighteen percent of enrolled patients had a PD-L1 combined positive score below 1, and 36% had received at least two lines of systemic therapy. The primary endpoint of this trial was the number of patients experiencing adverse events and dose-limiting toxicities. The median follow-up time was 26.5 months. The investigators stratified the outcomes according to the best overall response to quantify the impact of treatment depth.
Results: Median overall survival and median progression-free survival were not reached in patients achieving a complete response. The 12-month progression-free survival rate for patients with a complete response was 84.6% (P < 0.0001). The 24-month overall survival rate was 100.0% (P = 0.0002). Patients achieving a partial response also showed good prognosis, with median overall survival not yet reached, and a 24-month overall survival rate of 63% (P = 0.0002). The median progression-free survival in this group was 11.17 months, and the 12-month progression-free survival rate was 47.3% (P < 0.0001). The median duration of response was similar in the complete and partial response groups, at 1.84 months and 1.87 months, respectively. The median duration of response in the complete response group was not yet reached. Regardless of PD-L1 expression status, cadonilimab monotherapy achieved a median overall survival of 17.5 months in the overall population (95% CI, 11.4 months to not estimable); the 18-month and 24-month overall survival rates were 47.8% and 40.9%, respectively.
Common side effects include fatigue, nausea, rash, diarrhea, hypothyroidism, anemia, and infusion-related reactions. Grade 3 adverse events, such as pneumonia, colitis, or severe skin reactions, are usually manageable.
The findings were presented at the 27th European Congress of Gynecologic Oncology.
参考文献 Reference
Akeso. Press Release. March 2, 2026
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晚期乳腺癌一线与二线 CDK4/6 抑制剂对总生存期无差别 (3/1/2026)
First-line vs second-line CDK4/6 inhibitor does not impact overall survival in advanced breast cancer: SONIA trial
目的：确定一线 CDK4/6i 治疗激素受体阳性, ERBB2 阴性的晚期乳腺癌在总生存期方面是否优于二线治疗，并对两线治疗后无进展生存期这一主要终点进行更新分析。SONIA 是一项在荷兰开展的多中心 III 期随机临床试验。既往未接受过晚期乳腺癌治疗的激素受体阳性, ERBB2 阴性的1,050 名晚期乳腺癌患者按 1:1 的比例随机分组，分别接受 CDK4/6i 联合一线或二线内分泌治疗。患者入组时间为2017年11月23日至2021年9月1日。本次预设更新分析的数据截止日期为2024年9月1日。数据分析时间为2025年2月至5月。
治疗方法：1) 一线治疗方案为芳香化酶抑制剂联合CDK4/6抑制剂，二线治疗方案为氟维司群（CDK4/6i一线组）；2) 二线治疗方案为芳香化酶抑制剂，二线治疗方案为氟维司群联合CDK4/6抑制剂（CDK4/6i二线组）。主要 终点为两线治疗后的无进展生存期。总生存期为关键次要终点，预设分析条件为所有患者均有3年或以上的随访时间。
结果：1,050例入组患者的中位年龄（四分位间距）为64（16）岁。共有524例患者随机分配至CDK4/6抑制剂一线治疗组，526例患者随机分配至CDK4/6抑制剂二线治疗组。中位随访时间为58.5个月（95% CI，57.0-60.9），共发生606例死亡（57.7%）。一线CDK4/6抑制剂治疗组的中位总生存期为47.9个月（95% CI，44.0-54.3），二线CDK4/6抑制剂治疗组的中位总生存期为48.1个月（95% CI，44.7-52.0）（风险比[HR]为0.91；95% CI，0.77-1.07；P = 0.24）。事后亚组分析提示，一线治疗在绝经前患者中具有总生存期获益（HR，0.53；95% CI，0.32-0.87），但在绝经后患者中未观察到此获益（HR，1.00；95% CI，0.84-1.19；交互作用 P = 0.01）。在停止二线治疗的患者中，一线治疗组 303 例中有 257 例（84.8%）和二线治疗组 360 例中有 303 例（84.2%）接受了后续抗癌治疗，两组的治疗模式相似。一线 CDK4/6 抑制剂治疗较二线治疗更易发生 3 级或以上不良事件（分别为 3400 例和 2242 例）。
结论与意义：在这项3期随机临床试验中，一线CDK4/6抑制剂治疗激素受体阳性, ERBB2 阴性的晚期乳腺癌与二线治疗相比并未改善总生存期，反而增加了治疗相关毒性。事后分析表明，一线治疗在绝经前患者中可能具有总生存期获益。
Objective: To determine whether first-line CDK4/6i treatment for hormone receptor-positive, ERBB2-negative advanced breast cancer is superior to second-line treatment in terms of overall survival, and to update the analysis of the primary endpoint of progression-free survival after two lines of treatment. SONIA was a multicenter phase III randomized clinical trial conducted in the Netherlands. A total of 1,050 patients with hormone receptor-positive, ERBB2-negative advanced breast cancer who had not previously received treatment were randomized 1:1 to receive either CDK4/6i in combination with first-line or second-line endocrine therapy. Patient enrollment was from November 23, 2017 to September 1, 2021. The data cutoff date for this pre-specified update analysis was September 1, 2024. The data analysis period was from February to May 2025.
Treatment protocols: 1) First-line treatment was aromatase inhibitor combined with CDK4/6 inhibitor, and second-line treatment was fulvestrant (CDK4/6i first-line group); 2) Second-line treatment was aromatase inhibitor, and second-line treatment was fulvestrant combined with CDK4/6 inhibitor (CDK4/6i second-line group). The primary endpoint was progression-free survival after two lines of treatment. Overall survival was the key secondary endpoint, and the pre-specified analysis condition was that all patients had a follow-up period of 3 years or more.
Results: The median age (interquartile range) of the 1,050 enrolled patients was 64 (16) years. A total of 524 patients were randomly assigned to the CDK4/6 inhibitor first-line treatment group, and 526 patients were randomly assigned to the CDK4/6 inhibitor second-line treatment group. The median follow-up time was 58.5 months (95% CI, 57.0–60.9), with a total of 606 deaths (57.7%). The median overall survival in the first-line CDK4/6 inhibitor group was 47.9 months (95% CI, 44.0–54.3), and the median overall survival in the second-line CDK4/6 inhibitor group was 48.1 months (95% CI, 44.7–52.0) (hazard ratio [HR] 0.91; 95% CI, 0.77–1.07; P = 0.24). Post-hoc subgroup analyses suggested that first-line treatment had an overall survival benefit in premenopausal patients (HR, 0.53; 95% CI, 0.32–0.87), but this benefit was not observed in postmenopausal patients (HR, 1.00; 95% CI, 0.84–1.19; interaction P = 0.01). Among patients who discontinued second-line therapy, 257 out of 303 (84.8%) in the first-line therapy group and 303 out of 360 (84.2%) in the second-line therapy group received subsequent anticancer treatment, with similar treatment modalities between the two groups. First-line CDK4/6 inhibitor therapy was more likely to cause grade 3 or higher adverse events than second-line therapy (3400 cases vs. 2242 cases, respectively).
Conclusion: In this phase 3 randomized clinical trial, first-line CDK4/6 inhibitor therapy did not improve overall survival compared to second-line therapy in hormone receptor-positive, ERBB2-negative advanced breast cancer patients; instead, it increased treatment-related toxicities. Post-hoc analysis suggests that first-line therapy may have an overall survival benefit in premenopausal patients.
参考文献 Reference
Wortelboer N et al. JAMA Onc 2026, Feb 19th. doi: 10.1001/jamaoncol.2025.6585
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微塑料与前列腺癌 (2/28/2026)
Microplastics and prostate cancer
被称为微塑料和纳米塑料（MNPs）的微小塑料颗粒在许多人体组织中被发现。一项针对接受颈动脉内膜切除术患者的研究发现，斑块中含有MNPs的患者发生心肌梗死, 中风或死亡的风险是其他患者的4.5倍。本研究旨在确定人类前列腺癌组织中是否存在MNPs，并比较肿瘤组织和良性组织中MNPs的含量。
方法： 研究者招募了10例接受根治性前列腺切除术的前列腺癌患者。前列腺切除标本置于金属容器中运输，并由泌尿病理学家进行无塑料病理评估。随后，将前列腺肿瘤组织和前列腺其他部位的良性组织样本分别送至实验室，采用两种不同的技术进行微塑料颗粒评估：（1）结合拉曼显微镜进行目视检查，以评估MNP颗粒的丰度, 大小和其他特征；（2）采用热解-气相色谱/质谱联用（py-GC/MS）技术，以质量为基础鉴定和定量MNP。研究者使用描述性统计方法统计了所鉴定MNP的类型和浓度。
结果： 使用拉曼显微镜，在60%的患者样本中检测到了微塑料颗粒，单个颗粒的直径范围为1.2 µm至40.3 µm。肿瘤组织样本中的颗粒数量多于良性组织。使用Py-GC/MS技术，在90%的患者样本中发现了MNP（90%的肿瘤组织和70%的邻近良性组织）。肿瘤组织中微塑料的浓度往往高于肿瘤周围组织。肿瘤组织中微塑料颗粒的平均浓度为39.8 µg/g（中位数为16.3 µg/g），而邻近良性组织中的平均浓度为15.5 µg/g（中位数为7.0 µg/g）。就颗粒类型而言，使用 py-GC/MS 技术在大多数样本中检测到了高于方法检测限的尼龙-6和聚苯乙烯，而拉曼光谱法也检测到了聚乙烯和聚乙烯共聚物。
结论： 使用两种方法均在10例前列腺癌患者中的9例的组织样本中检测到了微塑料，且肿瘤组织中的浓度高于良性组织。
Tiny plastic particles, known as microplastics and nanoplastics (MNPs), have been found in many human tissues. A study of patients undergoing carotid endarterectomy found that patients with plaques containing MNPs had a 4.5 times higher risk of myocardial infarction, stroke, or death than other patients. This study aimed to determine the presence of MNPs in human prostate cancer tissue and to compare the content of MNPs in tumor tissue and benign tissue.
Methods: Ten patients with prostate cancer who underwent radical prostatectomy were recruited. Prostatectomy specimens were transported in metal containers and evaluated for plastic-free pathology by urologists. Subsequently, prostate tumor tissue and benign tissue samples from other parts of the prostate were sent to the laboratory for microplastic particle evaluation using two different techniques: (1) visual examination combined with Raman microscopy to assess the abundance, size, and other characteristics of MNP particles; and (2) mass-based identification and quantification of MNPs using pyrolysis-gas chromatography/mass spectrometry (py-GC/MS). The types and concentrations of the identified MNPs were statistically analyzed using descriptive statistical methods.
Results: Microplastic particles (MNPs) were detected in 60% of patient samples using Raman microscopy, with individual particle diameters ranging from 1.2 µm to 40.3 µm. The number of particles was higher in tumor tissue samples than in benign tissue. MNPs were detected in 90% of patient samples (90% of tumor tissue and 70% of adjacent benign tissue) using Py-GC/MS. The concentration of microplastics in tumor tissue was generally higher than in surrounding tumor tissue. The mean concentration of MNPs in tumor tissue was 39.8 µg/g (median 16.3 µg/g), while the mean concentration in adjacent benign tissue was 15.5 µg/g (median 7.0 µg/g). Regarding particle type, nylon-6 and polystyrene were detected above the method detection limit in most samples using py-GC/MS, while polyethylene and polyethylene copolymers were also detected by Raman spectroscopy.
Conclusion: Microplastics were detected in tissue samples from 9 out of 10 prostate cancer patients using both methods, and the concentration in tumor tissue was higher than that in benign tissue.
参考文献 Reference
Loeb S. J Clin Oncol 44, 2026 (suppl 7; abstr 379)
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FDA 已批准 amivantamab-vmjw (皮下注射)联合 lazertinib作为一线疗法用于晚期 EGFR突变型非小细胞肺癌 (2/22/2026)
The FDA has approved (subcutaneous) amivantamab-vmjw in combination with lazertinib as a first-line treatment for advanced EGFR-mutant non-small cell lung cancer
该决定基于III 期 MARIPOSA 试验的数据， MARIPOSA 是一项国际性随机试验，纳入了年龄至少 18 岁、既往未接受治疗的局部晚期或转移性非小细胞肺癌患者，这些患者携带 EGFR 19 号外显子缺失或 21 号外显子 L858R 突变。允许患者存在无症状或稳定的脑转移。患者按 2:2:1 的比例随机分配至三组，分别接受 amivantamab 联合 Lazertinib 治疗, 奥希替尼（Tagrisso）单药治疗或 Lazertinib 单药治疗。Amivantamab 的给药剂量为 1050 mg（体重至少 80 kg 的患者为 1400 mg），每周一次，持续 4 周，其中首次输注分 2 天进行（第 1 个周期第 1 天输注 350 mg，剩余部分在第 1 个周期第 2 天输注）。从第 2 个周期开始，amivantamab 每 2 周给药一次。每日一次，分别给予奥希替尼 80 mg 和 Lazertinib 240 mg。 根据 RECIST 1.1 标准，由独立中心审查机构进行盲法评估，比较联合治疗组与奥希替尼单药治疗组的无进展生存期，作为该试验的主要终点。次要终点包括总生存期, 客观响应率, 响应持续时间和安全性。
该试验显示，与奥希替尼相比，amivantamab 联合 lazertinib 可降低30%的疾病进展或死亡风险（HR，0.70；95% CI，0.58-0.85；P < .001）。接受联合治疗的患者（n = 429）的中位无进展生存期为 23.7 个月，而接受奥希替尼治疗的患者（n = 429）的中位无进展生存期为 16.6 个月。联合治疗的客观响应率为 86%（95% CI，83%-89%），而奥希替尼组的客观响应率为 85%（95% CI，81%-88%）。试验组的响应持续时间为 25.8 个月（95% CI，20.1–无法估计 [NE]），而对照组为 16.8 个月（95% CI，14.8-18.5）。联合治疗组和奥希替尼单药治疗组的中位无进展生存期均未达到统计学意义（HR，0.80；95% CI，0.61-1.05）。试验组的 18 个月和 24 个月总生存率分别为 82%（95% CI，78%-85%）和 74%（95% CI，69%-78%）。在奥希替尼组中，这些发生率分别为 79%（95% CI，75%-83%）和 69%（95% CI，64%-74%）。
关于安全性，接受联合治疗的患者中，至少 20% 报告的最常见不良反应包括皮疹, 指甲毒性, amivantamab 输注相关反应, 肌肉骨骼疼痛, 水肿, 口腔炎, 静脉血栓栓塞, 感觉异常, 疲乏, 腹泻, 便秘, COVID-19 感染, 出血, 皮肤干燥, 食欲下降, 瘙痒, 恶心和眼毒性。 lazertinib联合 amivantamab 治疗期间观察到静脉血栓栓塞事件，FDA 建议在治疗的前 4 个月进行预防性抗凝治疗。 Lazertinib 的推荐剂量为每日一次，每次240毫克，可与amivantamab单抗联合使用，餐前或餐后服用均可。Amivantamab 的推荐剂量取决于患者的基线体重。
This decision was based on data from the phase III MARIPOSA trial, an international randomized trial that enrolled patients at least 18 years of age with previously untreated locally advanced or metastatic non-small cell lung cancer carrying EGFR exon 19 deletion or exon 21 L858R mutation. Asymptomatic or stable brain metastases were permitted. Patients were randomized 2:2:1 to three groups to receive amivantamab in combination with lazertinib, osimertinib (Tagrisso) monotherapy, or lazertinib monotherapy. Amivantamab was administered at a dose of 1050 mg (1400 mg for patients weighing at least 80 kg) once weekly for 4 weeks, with the first infusion administered over two days (350 mg on day 1 of cycle 1, and the remainder on day 2 of cycle 1). Starting from cycle 2, amivantamab was administered every 2 weeks. Osimertinib 80 mg and lazertinib 240 mg were administered once daily. The primary endpoint of the trial was progression-free survival, compared to osimertinib monotherapy, in a blinded, independent central review setting according to RECIST 1.1 criteria. Secondary endpoints included overall survival, objective response rate, duration of response, and safety.
The trial demonstrated that, compared to osimertinib, amivantamab in combination with lazertinib reduced the risk of disease progression or death by 30% (HR, 0.70; 95% CI, 0.58–0.85; P < .001). The median progression-free survival was 23.7 months in patients receiving combination therapy (n = 429) and 16.6 months in patients receiving osimertinib alone (n = 429). The objective response rate (ORR) for combination therapy was 86% (95% CI, 83%–89%), while the ORR for osimertinib was 85% (95% CI, 81%–88%). The duration of response was 25.8 months (95% CI, 20.1–not estimable [NE]) in the experimental group and 16.8 months (95% CI, 14.8–18.5) in the control group. Median progression-free survival was not statistically significant in either the combination therapy or osimertinib monotherapy groups (HR, 0.80; 95% CI, 0.61–1.05). The 18-month and 24-month overall survival rates in the experimental groups were 82% (95% CI, 78%–85%) and 74% (95% CI, 69%–78%), respectively. In the osimertinib group, these incidence rates were 79% (95% CI, 75%–83%) and 69% (95% CI, 64%–74%), respectively.
Regarding safety, the most common adverse reactions reported in at least 20% of patients receiving combination therapy included rash, nail toxicity, amivantamab infusion-related reactions, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, bleeding, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. Venous thromboembolic events have been observed during lazertinib in combination with amivantamab, and the FDA recommends prophylactic anticoagulation therapy for the first 4 months of treatment. The recommended dose of lazertinib is 240 mg once daily, which can be used in combination with amivantamab monoclonal antibody, taken before or after meals. The recommended dose of amivantamab depends on the patient’s baseline weight.
参考文献 Reference
https://www.onclive.com/view/fda-approves-subcutaneous-amivantamab-for-egfr-nsclc
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术前放疗或可改善乳腺癌的抗肿瘤免疫反应 (2/21/2026)
Preoperative radiation may improve antitumor immune response in breast cancer
这是一项 II 期临床试验（P-RAD, NCT04443348），患者为雌激体阳性, HER2阴性且已扩散至区域淋巴结。中位年龄为49.5岁，年龄范围为23至78岁。51名患者按1:1:1的比例随机分配至三个组：不接受放射治疗组（0 Gy）, 接受低剂量放射治疗（9 Gy）组和接受高剂量放射治疗（24 Gy）组，所有患者均在开始化疗前接受帕博利珠单抗治疗。放射治疗分三天进行。 所有患者均接受了为期 12 周的帕博利珠单抗联合紫杉醇治疗，随后接受了 4 个周期的帕博利珠单抗联合多柔比星和环磷酰胺治疗。研究人员评估了两个共同主要终点：放疗后两周活检时的T细胞浸润值，以及根治性手术切除肿瘤时淋巴结的病理完全响应 (ypN0)。次要终点包括病理完全响应 (pCR) 和残余肿瘤负荷。
在接受放疗和免疫治疗后，在 49 例可评估T细胞浸润的患者中，T细胞浸润值最高四分位数的肿瘤比例随放疗剂量的增加而增加：0 Gy 组为 31%，9 Gy 组为 40%，24 Gy 组为 53%。 所有患者接受治疗后，T细胞浸润中位数均有所增加，这意味着放疗使更多 T 细胞进入并攻击肿瘤。然而，只有接受 24 Gy 治疗的患者在肿瘤控制指数 (T细胞浸润) 方面较未治疗肿瘤有统计学意义上的显著改善。 在所有 48 例可评估患者中，手术切除淋巴结的肿瘤清除率为 29%，并随放射剂量的增加而呈上升趋势：0 Gy 组为 24%，9 Gy 组为 29%，24 Gy 组为 33%。 次要终点指标也随着放射剂量的增加而改善。所有患者的病理完全响应率和残余肿瘤负荷率分别为 18% 和 27%。按治疗组划分，0 Gy 组分别为 6% 和 18%；9 Gy 组分别为 29% 和 29%；24 Gy 组分别为 19% 和 33%。由于患者数量有限，这些手术响应率的差异未达到统计学意义。
初步证据表明，三天内给予24 Gy的聚焦放射剂量，并联合帕博利珠单抗治疗，可以增强免疫活性，并可能改善术前肿瘤清除率。
This was a phase II clinical trial (P-RAD, NCT04443348) in patients who were estrogen-positive, HER2-negative, and the tumor had spread to regional lymph nodes. The median age was 49.5 years, ranging from 23 to 78 years. Fifty-one patients were randomized 1:1:1 to three groups: no radiation therapy (0 Gy), low-dose radiation therapy (9 Gy), and high-dose radiation therapy (24 Gy). All patients received pembrolizumab prior to chemotherapy. Radiation therapy was administered over three days. All patients received 12 weeks of pembrolizumab plus paclitaxel, followed by four cycles of pembrolizumab plus doxorubicin and cyclophosphamide. Researchers assessed two co-primary endpoints: T-cell infiltration at biopsy two weeks after radiation therapy and pathological complete response (ypN0) of lymph nodes at radical surgical resection of the tumor. Secondary endpoints included pathological complete response (pCR) and residual tumor burden.
Following radiotherapy and immunotherapy, in 49 evaluable patients with T-cell infiltration, the proportion of tumors in the highest quartile of T-cell infiltration values increased with increasing radiation dose: 31% in the 0 Gy group, 40% in the 9 Gy group, and 53% in the 24 Gy group. The median T-cell infiltration increased in all patients after treatment, indicating that radiotherapy induced more T cells to enter and attack the tumor. However, only patients receiving 24 Gy treatment showed a statistically significant improvement in the tumor control index (T-cell infiltration) compared to untreated tumors. In all 48 evaluable patients, the tumor clearance rate from surgically resected lymph nodes was 29%, trending upwards with increasing radiation dose: 24% in the 0 Gy group, 29% in the 9 Gy group, and 33% in the 24 Gy group. Secondary endpoints also improved with increasing radiation dose. The pathological complete response rate and residual tumor burden were 18% and 27% for all patients, respectively. By treatment group, the rates were 6% and 18% in the 0 Gy group, 29% and 29% in the 9 Gy group, and 19% and 33% in the 24 Gy group. Due to the limited number of patients, these differences in surgical response rates were not statistically significant.
Preliminary evidence suggests that a 24 Gy focused radiation dose administered over three days, in combination with pembrolizumab, may enhance immune activity and potentially improve preoperative tumor clearance.
参考文献 Reference
Gupta G et al. 2025 San Antonio Breast Cancer Symp Abstr GS2-05
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奥拉帕尼单药治疗携带 PALB2 生殖系突变或 BRCA1/BRCA2 体细胞突变的转移性乳腺癌 (2/15/2026)
Olaparib monotherapy for metastatic breast cancer with germline mutations in PALB2 or somatic mutations in BRCA1/BRCA2: TBCRC 048 trial
本研究报告了携带生殖系 PALB2 突变或体细胞 (s) BRCA 突变 (sBRCAm) 的患者的扩展队列研究结果。
方法: 符合条件的患者为任何亚型的转移性乳腺癌，且具有可测量病灶，并携带生殖系 PALB2突变或 sBRCAm。患者接受奥拉帕尼 300 mg 每日两次治疗，直至疾病进展。主要终点为总响应率。次要终点包括 18 周时的临床获益率, 无进展生存期, 响应持续时间以及 sBRCAm 携带者中，响应者突变等位基因频率 (MAF) 是否显著高于非响应者。
结果: 共纳入 54 例患者，其中生殖系 PALB2突变患者 24 例，sBRCAm 患者 30 例。 42例（78%）为雌激素受体阳性、人表皮生长因子受体2阴性（HER2-）转移性乳腺癌，7例（13%）为三阴性乳腺癌，5例（9%）为HER2阳性乳腺癌。在携带生殖系 PALB2突变的患者中，总响应率为75%（80% CI，60.2%至86.3%），临床获益率为83.3%（90% CI，65.8%至94.1%），中位无进展生存期（PFS）为9.4个月（90% CI，8.3个月至13.1个月），中位响应持续时间为7.0个月（90% CI，5.6个月至10.4个月）。在携带 sBRCAm 的患者（15 例 sBRCA1 和 15 例 sBRCA2）中，客观响应率为 36.7%（80% CI，24.7% 至 50%），临床获益率 (CBR) 为 53.3%（90% CI，37% 至 69.1%），中位无进展生存期为 5.5 个月（90% CI，2.8 个月至 8.3 个月），中位响应持续时间为 11.2 个月（90% CI，4.4 个月至未达到）。另有 1 例患者出现未经确认的部分响应。尽管具有临床意义，但携带 sBRCAm 患者的客观响应率并未达到预设目标。在 sBRCAm 携带者中，响应者 (46%) 和无响应者 (39%) 的平均次要等位基因频率无显著差异（P = 0.7）。
结论: 奥拉帕尼对携带生殖系 PALB2突变和 sBRCAm 的转移性乳腺癌患者有效，显著扩大了除 生殖系 BRCA1/2突变携带者之外，可能从 PARP 抑制剂中获益的乳腺癌患者群体。
This study reported the results of an expanded cohort study of patients carrying germline PALB2 mutations or somatic (s)BRCA mutations (sBRCAm).
Methods: Eligible patients were those with any subtype of metastatic breast cancer, measurable lesions, and carrying germline PALB2 mutations or sBRCAm. Patients received olaparib 300 mg twice daily until disease progression. The primary endpoint was overall response rate. Secondary endpoints included clinical benefit at 18 weeks, progression-free survival, duration of response, and whether the mutational allele frequency (MAF) was significantly higher in responders than in non-responders among sBRCAm carriers.
Results: A total of 54 patients were included, of whom 24 had germline PALB2 mutations and 30 had sBRCAm. Of the 42 patients (78%) with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, 7 (13%) with triple-negative breast cancer and 5 (9%) with HER2-positive breast cancer, the overall response rate was 75% (80% CI, 60.2% to 86.3%), the clinical benefit rate was 83.3% (90% CI, 65.8% to 94.1%), the median progression-free survival (PFS) was 9.4 months (90% CI, 8.3 months to 13.1 months), and the median duration of response was 7.0 months (90% CI, 5.6 months to 10.4 months).
In patients carrying sBRCAm (15 sBRCA1 and 15 sBRCA2), the objective response rate was 36.7% (80% CI, 24.7% to 50%), the clinical benefit rate (CBR) was 53.3% (90% CI, 37% to 69.1%), the median progression-free survival was 5.5 months (90% CI, 2.8 months to 8.3 months), and the median duration of response was 11.2 months (90% CI, 4.4 months to not reached). One patient had an unconfirmed partial response. Despite its clinical significance, the objective response rate in sBRCAm carriers did not meet the pre-specified target. Among sBRCAm carriers, there was no significant difference in mean minor allele frequencies between responders (46%) and non-responders (39%) (P = 0.7).
Conclusion: Olaparib is effective in patients with metastatic breast cancer carrying germline PALB2 mutations and sBRCAm, significantly expanding the pool of breast cancer patients who may benefit from PARP inhibitors, in addition to germline BRCA1/2 mutation carriers.
参考文献 Reference
Tung NM et al. J Clin Onc 2026; DOI: 10.1200/JCO-25-02075
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溶瘤病毒激活免疫系统对抗胶质母细胞瘤 (2/14/2026)
Oncolytic viruses activate the immune system to treat glioblastoma
方法: 研究人员开展了一项首次人体开放标签的 I 期临床试验（NCT03152318），评估单次胶质母细胞瘤内注射rQNestin34.5v.2（经基因工程改造可选择性在胶质母细胞瘤细胞中复制的溶瘤性单纯疱疹病毒）的疗效。 该研究纳入了41例复发性胶质母细胞瘤患者，
结果: 患者生存期显著延长，尤其是在存在预先病毒抗体的患者中。 进一步分析了溶瘤病毒在肿瘤微环境中的免疫激活情况, 空间免疫谱以及临床疗效后, 研究人员发现，溶瘤病毒治疗可扩增预先存在的T细胞克隆，并产生针对胶质母细胞瘤细胞的持续性T细胞介导免疫。 解型 caspase-3+ 肿瘤细胞与颗粒酶 B+ T 细胞之间的距离越短，溶瘤病毒治疗后患者的无进展生存期就越长。此外，当先前浸润肿瘤的 T 细胞在治疗后扩增时，可延长患者的总生存期。 尽管病毒残余物仍停留在坏死区域，但 T 细胞会浸润到存活的肿瘤区域。 当攻击肿瘤细胞的 T 细胞浸润增加，可转化为胶质母细胞瘤患者的治疗获益，
这些数据表明，单次溶瘤病毒治疗可以扩增预先存在的 T 细胞克隆，并引发针对胶质母细胞瘤的持久性 T 细胞介导免疫。
Methods: Researchers conducted a first-in-human open-label phase I clinical trial (NCT03152318) to evaluate the efficacy of a single intratumoral injection of rQNestin34.5v.2 (a genetically engineered oncolytic herpes simplex virus that selectively replicates in glioblastoma cells). The study included 41 patients with recurrent glioblastoma.
Results: Patient survival was significantly prolonged, especially in patients with pre-existing viral antibodies. Further analysis of oncolytic virus immune activation in the tumor microenvironment, spatial immune profile, and clinical efficacy revealed that oncolytic virus treatment amplifies pre-existing T-cell clones and generates persistent T-cell-mediated immunity against glioblastoma cells. The shorter the distance between dissociated caspase-3+ tumor cells and granzyme B+ T cells, the longer the progression-free survival after oncolytic virus treatment. Furthermore, when previously tumor-infiltrating T cells expand after treatment, overall survival was prolonged. Although viral remnants remain in necrotic areas, T cells infiltrate surviving tumor regions. Increased infiltration of tumor-attacking T cells can translate into treatment benefit.
These data suggest that a single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against glioblastoma.
参考文献 Reference
Meylan M et al. Cell 2026 ; Feb 11
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新型 CDK2抑制剂 INCB123667 用于铂类耐药性卵巢癌(2/8/2026)
A novel CDK2 inhibitor INCB123667 for platinum-resistant ovarian cancer
这是一项 I 期临床试验，参加者患有铂耐药或难治性上皮性卵巢癌, 输卵管癌或原发性腹膜癌，且此前接受过最多 4 线全身治疗。其他入选标准包括经当地实验室或中央实验室确认的 CCNE1 基因扩增或细胞周期蛋白 E1 过表达，以及 ECOG 体能状态评分为 0 或 1。 该研究的主要目标是评估 INCB123667 单药治疗的安全性和耐受性，并确定最大耐受剂量和推荐剂量。次要目标包括客观响应率, 疾病控制率和响应持续时间。
方法: INCB123667 的起始剂量为每日 50 mg，剂量递增至每日 150 mg。该研究纳入了 90 例卵巢癌患者，其中 1a 部分和 1b 部分各纳入 45 例患者。公布的主要疗效数据来自 1b 部分的 45 例患者，其中 30 例患者接受了最佳剂量 100 mg/天的治疗。 在全部 90 例患者中，中位年龄为 62.0 岁（范围：37.0-80.0 岁），其中 34.4%（n = 31）的患者年龄在 65 岁或以上。大多数患者的组织学类型为浆液性癌（80.0%；n = 72），少数患者为透明细胞癌（5.6%；n = 5）, 子宫内膜样癌（1.1%；n = 1）或其他组织学亚型（13.3%；n = 12）。92.2%的患者（n = 83）观察到细胞周期蛋白E1过表达，56.7%的患者（n = 51）存在CCNE1基因扩增。患者此前平均接受过4种（范围：1-12种）全身治疗，其中68.9%（n = 62）的患者曾接受过PARP抑制剂治疗，76.7%（n = 69）的患者曾接受过贝伐珠单抗治疗。
关于安全性，INCB123667 的不良事件被认为是可控的。治疗期间出现的不良事件主要为血液系统和胃肠道不良事件，且主要为 ≤2 级。仅 2.2% 的患者因不良事件停药。
结果显示，在最佳治疗剂量100 mg/天时，INCB123667的客观响应率为33.3%（30例患者中有10例），超过70%的患者肿瘤体积较基线缩小。中位响应时间为2.1个月（范围：1.6-7.7个月），中位响应持续时间为3.6个月（范围：1.9个月-未达到）。中位无进展生存期为5.3个月。值得注意的是，除1例患者外，所有响应者均存在细胞周期蛋白E1过表达。 中位治疗持续时间为4.5个月（范围：0.1-18.1个月）。截至2025年3月10日数据截止日期，共有8例患者（8.9%）仍在接受治疗。其余82例患者（91.1%）已停止治疗，最常见的原因是疾病进展（n = 70；77.8%）。另有3例患者（3.3%）因不良事件停止治疗 。
This was a phase I clinical trial involving participants with platinum-resistant or refractory epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who had previously received up to four lines of systemic therapy. Other inclusion criteria included CCNE1 gene amplification or cyclin E1 overexpression confirmed by a local or central laboratory, and an ECOG performance status of 0 or 1. The primary objective of the study was to assess the safety and tolerability of INCB123667 monotherapy and to determine the maximum tolerated dose and recommended dose. Secondary objectives included objective response rate, disease control rate, and duration of response.
Methods: The starting dose of INCB123667 was 50 mg daily, with dose escalation up to 150 mg daily. The study enrolled 90 ovarian cancer patients, with 45 patients in each of parts 1a and 1b. The primary efficacy data presented are from the 45 patients in part 1b, of whom 30 received the optimal dose of 100 mg/day. Among all 90 patients, the median age was 62.0 years (range: 37.0-80.0 years), with 34.4% (n = 31) of patients aged 65 years or older. The majority of patients had serous carcinoma (80.0%; n = 72), with a smaller number having clear cell carcinoma (5.6%; n = 5), endometrioid carcinoma (1.1%; n = 1), or other histological subtypes (13.3%; n = 12). Cyclin E1 overexpression was observed in 92.2% of patients (n = 83), and CCNE1 gene amplification was present in 56.7% of patients (n = 51). Patients had previously received an average of 4 lines (range: 1-12) of systemic therapies, with 68.9% (n = 62) having received PARP inhibitors and 76.7% (n = 69) having received bevacizumab.
Regarding safety, adverse events with INCB123667 were considered manageable. Adverse events during treatment were primarily hematological and gastrointestinal, and mostly ≤ grade 2. Only 2.2% of patients discontinued treatment due to adverse events.
The results showed that at the optimal treatment dose of 100 mg/day, the objective response rate for INCB123667 was 33.3% (10 out of 30 patients), with over 70% of patients experiencing a reduction in tumor volume from baseline. The median time to response was 2.1 months (range: 1.6-7.7 months), and the median duration of response was 3.6 months (range: 1.9 months – not reached). The median progression-free survival was 5.3 months. Notably, all responders except one had cyclin E1 overexpression. The median duration of treatment was 4.5 months (range: 0.1-18.1 months). As of the data cutoff date of March 10, 2025, eight patients (8.9%) were still receiving treatment. The remaining 82 patients (91.1%) had discontinued treatment, most commonly due to disease progression (n = 70; 77.8%). Three patients (3.3%) discontinued treatment due to adverse events.
参考文献 Reference
Damian S et al. J Clin Onc 2025: 43 [suppl 17]: 5514
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Zanidatamab 联合化疗±tislelizumab 一线治疗HER2阳性晚期胃食管腺癌（2/7/26）
Zanidatamab + chemotherapy ± tislelizumab for first-line HER2-positive locally advanced gastroesophageal adenocarcinoma: HERIZON-GEA-01
HERIZON-GEA-01（NCT05152147）是一项全球性, 开放标签, III期临床试验，旨在比较zanidatamab（双靶向HER2双特异性抗体）联合化疗±tislelizumab（抗PD-1抗体）与曲妥珠单抗联合化疗一线治疗 HER2+ 晚期（局部晚期, 不可切除或转移性）胃食管腺癌的疗效。
方法： 符合条件的既往未经治疗的HER2+ 晚期患者（无论PD-L1状态如何）被随机分配（1:1:1）至 1) zanidatamab（1800 mg [<70 kg] / 2400 mg [≥70 kg] 静脉注射，每3周一次）+ tislelizumab（200 mg 静脉注射，每3周一次）+卡培他滨/奥沙利铂（CAPOX）或5-氟尿嘧啶/顺铂（FP）方案；2) zanidatamab + CAPOX或FP方案；或 3) 曲妥珠单抗 + CAPOX或FP方案。主要终点为经盲法独立中央评估的无进展生存期和总生存期。
结果： 914例患者被随机分组（2021年12月至2025年2月）。截至数据截止日期（2025年10月），中位随访时间为26个月。与曲妥珠单抗联合化疗相比（8.1个月, 7.0-8.9），Zanidatamab 联合 tislelizumab和化疗组含的无进展生存期（12.4个月, 9.8-18.5）显著延长（HR=0.63 (0.51, 0.78); P <0.0001）。Zanidatamab 联合 tislelizumab和化疗组的总生存期（26.8个月, 20.4-30.0）相对于19.2个月 (16.8-21.8) , 具有统计学意义（HR- 0.80 (0.64, 1.01 [Interim] P = 0.0564）。在首次中期分析中， zanidatamab联合化疗组的总生存期尚未达到统计学意义，但观察到有利于 zanidatamab 联合化疗的显著趋势。无进展生存期和总生存期的改善在主要亚组中均有所体现，包括按地区和PD-L1 TAP评分划分的亚组。
在接受zanidatamab + tislelizumab + 化疗的患者中，71.8%的患者发生≥3级治疗相关不良事件；接受zanidatamab + 化疗的患者中，59.0%的患者发生≥3级治疗相关不良事件；接受曲妥珠单抗 + 化疗的患者中，59.6%的患者发生≥3级治疗相关不良事件。在任何含有zanidatamab的治疗组中，发生率超过10%的≥3级治疗相关不良事件包括腹泻, 低钾血症和贫血；在曲妥珠单抗 + 化疗组中，发生率超过10%的≥3级治疗相关不良事件包括腹泻, 贫血, 中性粒细胞计数降低和血小板计数降低。因相关不良事件而停用HER2靶向治疗的患者比例分别为：zanidatamab + tislelizumab + 化疗组为11.9%，zanidatamab + 化疗组为8.5%，曲妥珠单抗 + 化疗组为 2.3%。 未观察到zanidatamab或tislelizumab的新的安全性信号。
结论： 与曲妥珠单抗 + 化疗相比，两种含有zanidatamab的治疗方案均显示出具有临床意义且统计学显著的无进展生存期延长。zanidatamab + tislelizumab + 化疗方案也提供了统计学显著且具有临床意义的总生存期获益。该试验仍在进行中，计划对zanidatamab + 化疗组进行进一步的总生存期分析。
HERIZON-GEA-01 (NCT05152147) is a global, open-label, phase III clinical trial designed to compare the efficacy of zanidatamab (a dual-targeting HER2 bispecific antibody) in combination with chemotherapy ± tislelizumab (an anti-PD-1 antibody) versus trastuzumab in combination with chemotherapy as first-line treatment for HER2-positive advanced (locally advanced, unresectable, or metastatic) gastric and gastroesophageal junction adenocarcinoma.
Methods: Eligible previously untreated HER2-positive advanced patients (regardless of PD-L1 status) were randomly assigned (1:1:1) to 1) zanidatamab (1800 mg [<70 kg] / 2400 mg [≥70 kg] intravenously every 3 weeks) + tislelizumab (200 mg intravenously every 3 weeks) + capecitabine/oxaliplatin (CAPOX) or 5-fluorouracil/cisplatin (FP) regimen; 2) zanidatamab + CAPOX or FP regimen; or 3) trastuzumab + CAPOX or FP regimen. The primary endpoints were progression-free survival and overall survival as assessed by blinded independent central review.
Results: 914 patients were randomized (December 2021 to February 2025). As of the data cutoff date (October 2025), the median follow-up time was 26 months. Progression-free survival was significantly longer in the zanidatamab plus tislelizumab and chemotherapy group (12.4 months, 9.8-18.5) compared to trastuzumab plus chemotherapy (8.1 months, 7.0-8.9) (HR=0.63, 0.51-0.78; P <0.0001). The overall survival in the zanidatamab combined with tislelizumab and chemotherapy group (26.8 months, 20.4-30.0) was statistically significant compared to 19.2 months (16.8-21.8) (HR = 0.80 (0.64, 1.01 [Interim] P = 0.0564). In the first interim analysis, the overall survival in the zanidatamab combined with chemotherapy group did not reach statistical significance, but a significant trend favoring zanidatamab combined with chemotherapy was observed. Improvements in progression-free survival and overall survival were observed in all major subgroups, including subgroups stratified by region and PD-L1 TAP score.
Among patients receiving zanidatamab + tislelizumab + chemotherapy, 71.8% experienced grade ≥3 treatment-related adverse events; among patients receiving zanidatamab + chemotherapy, 59.0% experienced grade ≥3 treatment-related adverse events; and among patients receiving trastuzumab + chemotherapy, 59.6% experienced grade ≥3 treatment-related adverse events. Grade ≥3 treatment-related adverse events with an incidence exceeding 10% in any treatment group containing zanidatamab included diarrhea, hypokalemia, and anemia; in the trastuzumab + chemotherapy group, grade ≥3 treatment-related adverse events with an incidence exceeding 10% included diarrhea, anemia, decreased neutrophil count, and decreased platelet count. The proportion of patients discontinuing HER2-targeted therapy due to related adverse events was 11.9% in the zanidatamab + tislelizumab + chemotherapy group, 8.5% in the zanidatamab + chemotherapy group, and 2.3% in the trastuzumab + chemotherapy group. No new safety signals were observed for either zanidatamab or tislelizumab.
Conclusion: Compared to trastuzumab + chemotherapy, both zanidatamab-containing treatment regimens showed clinically meaningful and statistically significant improvements in progression-free survival. The zanidatamab + tislelizumab + chemotherapy regimen also provided a statistically significant and clinically meaningful overall survival benefit. This trial is ongoing, and further overall survival analyses are planned for the zanidatamab + chemotherapy group.
参考文献 Reference
Elimova E. J Clin Oncol 2026; 44 [suppl 2; abstr LBA285]
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Imneskibart in combination with interleukin-2 demonstrates antitumor activity in melanoma and non-small cell lung cancer.
一项正在进行的 I/II 期临床试验 (NCT05267626) 的数据显示，Imneskibart (AU-007) 与低剂量皮下注射白介素-2 (IL-2) 联合用药，在免疫检查点抑制剂难治性黑色素瘤或非小细胞肺癌患者中，可产生显著且持久的抗肿瘤活性。截至2025年9月29日数据截止日期，imneskibart 1/2期研究的关键发现（包括针对免疫检查点抑制剂耐药性黑色素瘤和非小细胞肺癌的2期扩展队列）如下:
截至 2025 年 9 月 29 日的数据截止日期，已对 93 例不同类型癌症患者的抗肿瘤活性进行了评估。 接受 Imneskibart 联合白介素-2双药的免疫检查点抑制剂难治性黑色素瘤患者，其肿瘤体积显著且持久缩小。14例接受治疗的患者中，6例仍在接受治疗。其中，1例缩小48%（治疗14个月），1例缩小58%（治疗18个月以上），1例达到完全响应（治疗21个月以上）。
另有5例免疫检查点抑制剂难治性黑色素瘤患者接受了Imneskibart, 白介素-2和纳武利尤单抗三药联合治疗。该组患者的早期数据显示，对于既往接受过免疫检查点抑制剂双药治疗后病情进展的患者，该联合治疗方案初步显示出抗肿瘤活性。一项使用较低剂量白介素-2（45,000 IU/kg）的安全性导入试验已完成，未出现剂量限制性毒性。目前，该队列正在招募接受白介素-2推荐剂量（135,000 IU/kg）治疗的患者。在接受治疗的5名患者中，3名仍在接受治疗。
在既往接受过免疫检查点抑制剂治疗（无论是否联合化疗）失败的非小细胞肺癌患者中， 9名患者接受了伊美沙酮, 白介素-2和Bavencio 联合治疗，其中4名患者的肿瘤缩小。在这4名患者中，2名既往接受过PD-1靶向治疗后病情进展的患者，肿瘤分别缩小了43%和48%; 其中1名仍在接受治疗。
在其他实体瘤和癌症患者中，也观察到疗效。一名接受抗PD-L1治疗后病情进展的膀胱癌患者，目前已获得持续的代谢完全响应，且循环肿瘤DNA检测呈阴性。该患者已接受治疗近3年。一名接受过5种全身治疗后病情进展的鼻咽癌患者也获得了确诊的完全响应，接受治疗超过2年。
试验安全性结果 在1期和2期试验的所有队列中，均观察到轻度和可控的安全性特征。大多数药物相关不良事件为1/2级。最常见的3级或4级不良事件是短暂性淋巴细胞减少症（3-7天），且在任何患者中均未观察到与不良结局相关。短暂性淋巴细胞减少症是IL-2治疗的已知副作用。 一名接受imneskibart治疗并接受一剂低剂量皮下注射阿地白介素的患者出现了4级细胞因子释放综合征（CRS）。该患者在未使用托珠单抗的情况下，通过使用类固醇, 静脉输液和短暂的血管加压药物支持后症状得到缓解。
研究设计: 试验第一阶段已完成，第二阶段扩展研究正在招募患者。确定的推荐第二阶段剂量 (RP2D) 为每两周静脉注射 9 mg/kg 的 imneskibart，并联合在每个周期的第 1 天单次注射 135K IU/kg 的 aldesleukin。疗效评估在每个 8 周周期结束时进行，根据肿瘤生长动力学，患者有可能在新的周期开始时接受额外剂量的 aldesleukin。预计将于 2026 年年中获得完整数据。
编：Imneskibart 是一种人源 IgG1 单克隆抗体，可与白细胞介素-2 结合，并特异性阻断其与三聚体受体 CD25 亚基的相互作用，从而阻止调节性 T 细胞 (Treg) 的扩增。
Data from an ongoing phase I/II clinical trial (NCT05267626) shows that Imneskibart (AU-007) in combination with low-dose subcutaneous interleukin-2 (IL-2) produces significant and durable anti-tumor activity in patients with immune checkpoint inhibitor-refractory melanoma or non-small cell lung cancer. As of the data cutoff date of September 29, 2025, key findings from the Imneskibart phase 1/2 study (including the phase 2 expansion cohort for immune checkpoint inhibitor-resistant melanoma and non-small cell lung cancer) are as follows:
Anti-tumor activity has been evaluated in 93 patients with various types of cancer. Patients with immune checkpoint inhibitor-refractory melanoma treated with Imneskibart in combination with IL-2 showed significant and durable tumor volume reduction. Of the 14 patients treated, 6 are still receiving treatment. Among these, one patient experienced a 48% reduction (after 14 months of treatment), one experienced a 58% reduction (after more than 18 months of treatment), and one achieved a complete response (after more than 21 months of treatment).
Five additional patients with immune checkpoint inhibitor-refractory melanoma received triple combination therapy with Imneskibart, IL-2, and nivolumab. Early data from this group of patients shows preliminary anti-tumor activity in patients who had previously progressed after receiving dual immune checkpoint inhibitor therapy. A safety run-in trial using a lower dose of IL-2 (45,000 IU/kg) has been completed without dose-limiting toxicities. This cohort is currently enrolling patients receiving the recommended dose of IL-2 (135,000 IU/kg). Of the 5 patients treated, 3 are still receiving treatment.
In non-small cell lung cancer patients who had previously failed treatment with immune checkpoint inhibitors (with or without chemotherapy), 9 patients received combination therapy with imneskibart, interleukin-2, and Bavencio, and tumor shrinkage was observed in 4 of these patients. Of these 4 patients, 2 patients who had previously progressed after PD-1 targeted therapy showed tumor reductions of 43% and 48%, respectively; one of these patients is still receiving treatment.
Efficacy was also observed in other solid tumors and cancers. One bladder cancer patient who progressed after anti-PD-L1 treatment has achieved a sustained metabolic complete response, with negative circulating tumor DNA. This patient has been receiving treatment for nearly 3 years. A nasopharyngeal carcinoma patient who progressed after 5 lines of systemic therapy also achieved a confirmed complete response and has been receiving treatment for over 2 years.
Trial safety: Mild and manageable safety profiles were observed across all cohorts in the phase 1 and phase 2 trials. Most drug-related adverse events were grade 1/2. The most common grade 3 or 4 adverse event was transient lymphopenia (3-7 days), and no adverse outcomes were observed in any patient. Transient lymphopenia is a known side effect of IL-2 treatment. One patient receiving imneskibart and a single low-dose subcutaneous injection of aldesleukin experienced grade 4 cytokine release syndrome (CRS). This patient’s symptoms resolved with steroids, intravenous fluids, and transient vasopressor support without the use of tocilizumab.
Study Design: The first phase of the trial has been completed, and the second phase expansion study is currently enrolling patients. The recommended phase 2 dose (RP2D) is 9 mg/kg of imneskibart intravenously every two weeks, combined with a single injection of 135K IU/kg of aldesleukin on Day 1 of each cycle. Efficacy assessments are performed at the end of each 8-week cycle, and patients may receive additional doses of aldesleukin at the start of a new cycle based on tumor growth kinetics. Complete data are expected in mid-2026.
Editor: Imneskibart is a human IgG1 monoclonal antibody that
binds to interleukin-2 and specifically blocks its interaction with the CD25 subunit of the trimeric receptor, preventing regulatory T cell (Treg) expansion.
参考文献 Reference
BioSpace November 12, 2025. https://tinyurl.com/3jsvh6fz
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改进用于早期检测胰腺导管腺癌的血浆标志物 (1/31/2026)
Improving a plasma biomarker panel for early detection of pancreatic ductal adenocarcinoma
实验设计： 研究者使用质谱和 ELISA 技术对来自宾夕法尼亚大学 (Penn) 和梅奥诊所 (Mayo) 的血浆样本进行分析，发现早期（I/II 期）胰腺导管腺癌患者血浆中氨肽酶 N (ANPEP) 和聚合免疫球蛋白受体 (PIGR) 的水平高于对照组。在回顾性 II 期研究中，使用来自 Penn (n = 135) 和 Mayo (n = 537) 的不同阶段患者血浆样本以及健康或非恶性疾病对照组的样本，对 ANPEP 和 PIGR 以及先前获得的血小板反应蛋白 2 (THBS2) 和糖类抗原 19-9 (CA19-9) 数据进行了测试。
结果： 将健康对照组与 I/II 期胰腺导管腺癌患者进行比较，Penn/Mayo II 期研究的受试者工作特征曲线下面积 (AUC) 分别为 0.78 [95% 置信区间 (CI)，0.68–0.86]/0.80 (95% CI，0.74–0.85；ANPEP) 和 0.81 (95% CI，0.70–0.88)/0.86 (95% CI，0.82–0.90；PIGR)。在多变量模型中，CA19-9/THBS2/ANPEP, CA19-9/THBS2/PIGR 和 CA19-9/THBS2/ANPEP/PIGR 的 AUC 值在 Penn 研究中为 0.94 至 0.96，在 Mayo 研究中为 0.97。值得注意的是，四种标志物组合在 Mayo 研究中，I/II 期胰腺导管腺癌患者与对照组的 AUC 值为 0.87，I 至 IV 期胰腺导管腺癌患者与对照组的 AUC 值为 0.91。在特异性为 95% 的情况下，由 CA19-9 (≥35 U/mL), THBS2 (≥42 ng/mL), ANPEP (≥2,995 ng/mL) 和 PIGR (≥1,800 ng/mL) 组成的血浆生物标志物组合对胰腺导管腺癌 I 至 IV 期患者的灵敏度为 91.9%，对胰腺导管腺癌 I/II 期患者的灵敏度为 87.5%。
结论： 与健康人群或非恶性疾病患者相比，将 ANPEP 和 PIGR 添加到由 CA19-9 和 THBS2 组成的血浆生物标志物组合中，可以提高早期胰腺导管腺癌的检测率。
Experimental Design: Researchers used mass spectrometry and ELISA techniques to analyze plasma samples from the University of Pennsylvania (Penn) and the Mayo Clinic, have found that levels of aminopeptidase N (ANPEP) and polymeric immunoglobulin receptor (PIGR) were higher in the plasma of early-stage (stage I/II) pancreatic ductal adenocarcinoma patients compared to controls. In a retrospective phase II study, ANPEP and PIGR, along with previously obtained thrombospondin-2 (THBS2) and carbohydrate antigen 19-9 (CA19-9) data, were tested using plasma samples from patients at different stages from Penn (n = 135) and Mayo (n = 537), as well as samples from healthy or non-malignant disease controls.
Results: Comparing healthy controls to stage I/II pancreatic ductal adenocarcinoma patients, the area under the receiver operating characteristic curve (AUC) in the Penn/Mayo phase II study was 0.78 [95% confidence interval (CI), 0.68–0.86]/0.80 (95% CI, 0.74–0.85; ANPEP) and 0.81 (95% CI, 0.70–0.88)/0.86 (95% CI, 0.82–0.90; PIGR). In multivariate models, the AUC values for CA19-9/THBS2/ANPEP, CA19-9/THBS2/PIGR, and CA19-9/THBS2/ANPEP/PIGR ranged from 0.94 to 0.96 in the Penn study and 0.97 in the Mayo study. Notably, the combination of four markers yielded an AUC of 0.87 for stage I/II pancreatic ductal adenocarcinoma patients versus controls in the Mayo study, and an AUC of 0.91 for stage I to IV pancreatic ductal adenocarcinoma patients versus controls. At a specificity of 95%, the plasma biomarker panel consisting of CA19-9 (≥35 U/mL), THBS2 (≥42 ng/mL), ANPEP (≥2,995 ng/mL), and PIGR (≥1,800 ng/mL) showed a sensitivity of 91.9% for patients with stage I to IV pancreatic ductal adenocarcinoma and 87.5% for patients with stage I/II pancreatic ductal adenocarcinoma. Conclusion: Adding ANPEP and PIGR to the plasma biomarker panel consisting of CA19-9 and THBS2 can improve the detection rate of early-stage pancreatic ductal adenocarcinoma compared to healthy individuals or patients with non-malignant diseases.
参考文献 Reference
Krusen BM et al. Clin Cancer Res 2026 Jan 28 https://doi.org/10.1158/1078-0432.CCR-25-3297
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FDA批准Sevabertinib用于非鳞状非小细胞肺癌 (1/25/2026)
FDA approves Sevabertinib for non-squamous non-small cell lung cancer with HER2 TKD activating mutations
Sevabertinib是一种激酶抑制剂，用于治疗局部晚期或转移性非鳞状非小细胞肺癌，这些患者的肿瘤存在HER2酪氨酸激酶结构域（TKD）激活突变，且此前已接受过全身治疗。 FDA还批准了Oncomine Dx Target Test作为伴随诊断设备，用于辅助检测可能符合Sevabertinib治疗条件的非鳞状非小细胞肺癌患者的HER2 TKD激活突变。 疗效评估基于SOHO-01（NCT05099172）临床试验。这是一项开放标签, 单臂, 多中心, 多队列临床试验，纳入了既往接受过全身治疗且患有不可切除或转移性非鳞状非小细胞肺癌并存在HER2 TKD激活突变的患者，这些患者接受了Sevabertinib治疗。HER2激活突变在入组前由当地实验室通过肿瘤组织或血浆样本进行检测。 主要疗效终点指标为经独立盲法中心评估, 根据RECIST v1.1标准评估的确认客观响应率和响应持续时间。
在70例局部晚期或转移性非小细胞肺癌且存在HER2 TKD激活突变、既往接受过全身治疗但未接受过针对HER2突变靶向治疗的患者中，客观响应率为71%（95% CI：59，82），中位响应持续时间为9.2个月（95% CI：6.3，15.0），54%的响应患者响应持续时间≥6个月。在52例既往接受过包括HER2靶向抗体偶联药物在内的全身治疗的局部晚期或转移性HER2 酪氨酸激酶结构域激活突变非小细胞肺癌患者中，客观响应率为38%（95% CI：25，53），中位响应持续时间为7.0个月（95% CI：5.6，无法评估），60%的有效应答患者响应持续时间 ≥6个月。
说明书包含腹泻, 肝毒性, 间质性肺病/肺炎, 眼毒性, 胰酶升高和胚胎-胎儿毒性的警告和注意事项。 推荐剂量 推荐的sevabertinib剂量为20 mg，每日两次，口服，随餐服用，直至疾病进展或出现不可耐受的毒性。
Sevabertinib is a kinase inhibitor used to treat locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) in patients whose tumors have HER2 tyrosine kinase domain (TKD) activating mutations* and who have previously received systemic therapy. FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to aid in detecting HER2 TKD activating mutations in non-squamous NSCLC patients who may be eligible for Sevabertinib treatment. Efficacy was evaluated based on the SOHO-01 (NCT05099172) clinical trial. This was an open-label, single-arm, multicenter, multi-cohort clinical trial that enrolled patients with unresectable or metastatic non-squamous NSCLC with HER2 TKD activating mutations who had previously received systemic therapy and were treated with Sevabertinib. HER2 activating mutations were detected by local laboratories using tumor tissue or plasma samples prior to enrollment. The primary efficacy endpoints were confirmed objective response rate and duration of response, assessed by an independent blinded central review according to RECIST v1.1 criteria.
In 70 patients with locally advanced or metastatic NSCLC with HER2 TKD activating mutations who had previously received systemic therapy but not HER2-targeted therapy, the objective response rate was 71% (95% CI: 59, 82), the median duration of response was 9.2 months (95% CI: 6.3, 15.0), and 54% of responding patients had a duration of response ≥6 months. In 52 patients with locally advanced or metastatic NSCLC with HER2 TKD activating mutations who had previously received systemic therapy, including HER2-targeted antibody-drug conjugates, the objective response rate was 38% (95% CI: 25, 53), the median duration of response was 7.0 months (95% CI: 5.6, not estimable), and 60% of responding patients had a duration of response ≥6 months.
The prescribing information includes warnings and precautions regarding diarrhea, hepatotoxicity, interstitial lung disease/pneumonia, ocular toxicity, elevated pancreatic enzymes, and embryo-fetal toxicity.
Recommended Dosage: The recommended dose of sevabertinib is 20 mg twice daily, taken orally with food, until disease progression or unacceptable toxicity occurs.
*HER2 TKD activating mutations such as exon 20 insertion mutation and point mutations.
参考文献 Reference
https://www.bayer.com/en/us/news-stories/hyrnuo
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首创口服小分子PPARγ抑制剂治疗晚期尿路上皮癌 I 期试验 (1/24/2026)
A phase I trial of first-in-class oral small molecule PPARγ inhibitor for the treatment of advanced urothelial carcinoma
大约三分之二的晚期尿路上皮癌的特征是过氧化物酶体增殖物激活受体γ（PPARG）的高表达，FX-909是首个在此类疾病治疗中显示出临床活性的靶向PPARγ的小分子药物。
方法: 这是一项I期临床试验（NCT05929235），研究人员招募了 46 例晚期实体瘤患者，其中包括 36 例晚期尿路上皮癌患者。患者每日口服 FX-909，剂量范围为 30 mg 至 100 mg，每 28 天为一个周期。研究人员还进行了生物标志物分析，以评估肿瘤 PPARG 的表达水平，并进行了皮肤活检，以确认治疗引起的药效学变化。 最大耐受剂量确定为 70 mg；然而，较低剂量（30 mg 和 50 mg）显示出更好的耐受性，同时保持了相似的临床疗效。目前正在进行一项随机 Ib 期研究，旨在评估这些较低剂量 FX-909 在前瞻性生物标志物筛选的 PPARG 高表达晚期尿路上皮癌二线或二线以上治疗患者中的疗效。
发现: 在31例可评估疗效的晚期尿路上皮癌患者中，20例患者的PPARγ表达水平经免疫组织化学检测显示为高表达。最常见的3级或以上治疗相关不良反应包括贫血, 血小板计数降低和疲劳。其他常见的治疗相关不良反应包括腹泻和血糖升高。 研究人员发现，30 mg的较低剂量与较少严重副作用, 副作用发生时间较晚以及治疗中断或剂量减少的情况较少相关。
在这些患者中，14例患者接受FX-909治疗后肿瘤有所消退，其中4例患者确诊为部分响应。此外，1例PPARγ表达水平中等的患者获得完全响应，另1例基线时疾病无法测量的患者也获得完全响应。
总结: FX-909显示出良好的安全性，并且是首个靶向PPARγ并在晚期尿路上皮癌中显示出临床抗肿瘤活性的小分子药物。目前正在进行一项随机Ib期研究。
Approximately two-thirds of advanced urothelial carcinoma cases are characterized by high expression of peroxisome proliferator-activated receptor gamma (PPARG). FX-909 is the first small molecule drug targeting PPARγ to demonstrate clinical activity in the treatment of this disease.
Methods: This was a phase I clinical trial (NCT05929235) that enrolled 46 patients with advanced solid tumors, including 36 patients with advanced urothelial carcinoma. Patients received oral FX-909 daily at doses ranging from 30 mg to 100 mg, in 28-day cycles. Biomarker analysis was performed to assess tumor PPARG expression levels, and skin biopsies were conducted to confirm treatment-induced pharmacodynamic changes. The maximum tolerated dose was determined to be 70 mg; however, lower doses (30 mg and 50 mg) showed better tolerability while maintaining similar clinical efficacy. A randomized phase Ib study is currently underway to evaluate the efficacy of these lower doses of FX-909 in patients with PPARG-high expressing advanced urothelial carcinoma in the second-line or later treatment setting, based on prospective biomarker screening.
Findings: Among the 31 evaluable patients with advanced urothelial carcinoma, 20 patients showed high PPARγ expression levels as determined by immunohistochemistry. The most common grade 3 or higher treatment-related adverse events included anemia, decreased platelet count, and fatigue. Other common treatment-related adverse events included diarrhea and hyperglycemia. The lower dose of 30 mg was associated with fewer severe side effects, later onset of side effects, and fewer treatment interruptions or dose reductions.
In these patients, 14 patients experienced tumor regression after treatment with FX-909, with 4 patients achieving a confirmed partial response. In addition, one patient with moderate PPARγ expression achieved a complete response, and another patient with unmeasurable disease at baseline also achieved a complete response.
Summary: FX-909 demonstrated a favorable safety profile and is the first small molecule drug targeting PPARγ to show clinical antitumor activity in advanced urothelial carcinoma.
参考文献 Reference
Gao X. et al. Presented at AACR-NCI-EORTC International Conference on Molecular Targets 2025; October 22
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Zanidatamab联合化疗一线治疗HER2阳性不可切除或转移性胃食管腺癌（1/18/2026）
Zanidatamab + chemotherapy ± for first-line HER2+ unresectable, or metastatic gastroesophageal adenocarcinoma: HERIZON-GEA-01
该试验旨在比较zanidatamab（双重HER2靶向双特异性抗体）联合化疗±tislelizumab（抗PD-1抗体）与曲妥珠单抗联合化疗一线治疗HER2+ 不可切除或转移性胃食管腺癌患者的疗效。
方法： 这是一项全球性, 开放标签、\, III期临床试验（HERIZON-GEA-01, NCT05152147），符合条件的既往未经治疗的HER2+ 不可切除或转移性胃食管腺癌患者（无论PD-L1状态如何）被随机分配（1:1:1）至1) zanidatamab（1800 mg [<70 kg] / 2400 mg [≥70 kg] 静脉注射，每3周一次）+ tislelizumab（200 mg 静脉注射，每3周一次）+卡培他滨/奥沙利铂（CAPOX）或5-氟尿嘧啶/顺铂（FP）方案；2) zanidatamab + CAPOX或FP方案；或3) 曲妥珠单抗 + CAPOX或FP方案。主要终点为经盲法独立中央评估的无进展生存期和总生存期。
结果： 914例患者被随机分组（2021年12月至2025年2月）。各组的人口统计学特征和基线疾病特征均衡。截至数据截止日期（2025年10月），在中位随访时间为 26 个月后，接受 zanidatamab 联合化疗（无论是否联合 tislelizumab）的患者的中位无进展生存期为 12.4 个月，而接受曲妥珠单抗治疗的患者的中位无进展生存期为 8.1 个月。 总体而言，zanidatamab 使癌症进展或死亡的风险降低了约 35%。 治疗 18 个月后，接受 zanidatamab、tislelizumab 和化疗的患者中约 44% 的癌症没有进展或扩散；接受 zanidatamab 和化疗的患者中 38% 的癌症没有进展或扩散；而曲妥珠单抗组中约 21% 的患者癌症没有进展或扩散。在首次中期分析中，zanidatamab联合化疗组的总生存期未达到统计学意义，但观察到有利于zanidatamab联合化疗的显著趋势。无进展生存期和总生存期的改善在主要亚组中均有所体现，包括按地区和PD-L1 TAP评分划分的亚组。
在接受 zanidatamab + tislelizumab + 化疗的患者中，71.8% 发生 ≥3 级治疗相关不良事件；接受 zanidatamab + 化疗的患者中，59.0% 发生 ≥3 级治疗相关不良事件；接受曲妥珠单抗 + 化疗的患者中，59.6% 发生 ≥3 级治疗相关不良事件。在任何包含 zanidatamab 的治疗组中，发生率 >10% 的 ≥3 级治疗相关不良事件包括腹泻, 低钾血症和贫血；在曲妥珠单抗 + 化疗组中，发生率 >10% 的 ≥3 级治疗相关不良事件包括腹泻, 贫血, 中性粒细胞计数降低和血小板计数降低。因相关不良事件而停用 HER2 靶向治疗的患者比例分别为：zanidatamab + tislelizumab + 化疗组 11.9%，zanidatamab + 化疗组 8.5%，曲妥珠单抗 + 化疗组 2.3%。
结论： 与曲妥珠单抗 + 化疗相比，两种包含 zanidatamab 的治疗方案均显示出具有临床意义且统计学显著的无进展生存期延长（中位无进展生存期 >12 个月）。Zanidatamab + tislelizumab + 化疗方案也提供了统计学显著且具有临床意义的总生存期获益（中位总生存期 >26 个月）。该试验仍在进行中，计划对 zanidatamab + 化疗组进行进一步的 总生存期 分析。未观察到 zanidatamab 或 tislelizumab 的新的安全性信号。这些结果支持 zanidatamab 作为 HER2 靶向药物的新标准。
This trial aimed to compare the efficacy of zanidatamab (a dual HER2-targeting bispecific antibody) in combination with chemotherapy ± tislelizumab (an anti-PD-1 antibody) versus trastuzumab in combination with chemotherapy as first-line treatment for patients with HER2-positive unresectable or metastatic gastroesophageal adenocarcinoma.
Methods: This was a global, open-label, phase III clinical trial (HERIZON-GEA-01, NCT05152147). Previously untreated patients with HER2-positive unresectable or metastatic gastroesophageal adenocarcinoma (regardless of PD-L1 status) were randomly assigned (1:1:1) to 1) zanidatamab (1800 mg [<70 kg] / 2400 mg [≥70 kg] intravenously every 3 weeks) + tislelizumab (200 mg intravenously every 3 weeks) + capecitabine/oxaliplatin (CAPOX) or 5-fluorouracil/cisplatin (FP) regimen; 2) zanidatamab + CAPOX or FP regimen; or 3) trastuzumab + CAPOX or FP regimen. The primary endpoints were progression-free survival and overall survival as assessed by blinded independent central review.
Results: 914 patients were randomized (December 2021 to February 2025). Demographic characteristics and baseline disease characteristics were balanced across the groups. As of the data cutoff date (October 2025), after a median follow-up of 26 months, the median progression-free survival was 12.4 months for patients receiving zanidatamab in combination with chemotherapy (with or without tislelizumab), compared to 8.1 months for patients receiving trastuzumaband chemotherapy. Overall, zanidatamab reduced the risk of cancer progression or death by approximately 35%. After 18 months of treatment, approximately 44% of patients receiving zanidatamab, tislelizumab, and chemotherapy had no cancer progression or spread; 38% of patients receiving zanidatamab and chemotherapy had no cancer progression or spread; and approximately 21% of patients in the trastuzumab group had no cancer progression or spread. In the first interim analysis, overall survival in the zanidatamab plus chemotherapy group did not reach statistical significance, but a significant trend favoring zanidatamab plus chemotherapy was observed. Improvements in progression-free survival and overall survival were observed across major subgroups, including subgroups stratified by region and PD-L1 TAP score.
Among patients receiving zanidatamab + tislelizumab + chemotherapy, 71.8% experienced grade ≥3 treatment-related adverse events; among patients receiving zanidatamab + chemotherapy, 59.0% experienced grade ≥3 treatment-related adverse events; and among patients receiving trastuzumab + chemotherapy, 59.6% experienced grade ≥3 treatment-related adverse events. Grade ≥3 treatment-related adverse events with an incidence >10% in any treatment group containing zanidatamab included diarrhea, hypokalemia, and anemia; in the trastuzumab + chemotherapy group, grade ≥3 treatment-related adverse events with an incidence >10% included diarrhea, anemia, decreased neutrophil count, and decreased platelet count. The proportion of patients discontinuing HER2-targeted therapy due to related adverse events was 11.9% in the zanidatamab + tislelizumab + chemotherapy group, 8.5% in the zanidatamab + chemotherapy group, and 2.3% in the trastuzumab + chemotherapy group.
Conclusion: Compared to trastuzumab + chemotherapy, both treatment regimens containing zanidatamab showed clinically meaningful and statistically significant improvements in progression-free survival (median progression-free survival >12 months). The zanidatamab + tislelizumab + chemotherapy regimen also provided a statistically significant and clinically meaningful overall survival benefit (median overall survival >26 months). The trial is ongoing, and further overall survival analyses are planned for the zanidatamab + chemotherapy group. No new safety signals were observed for either zanidatamab or tislelizumab. These results support zanidatamab as a new standard for HER2-targeted therapy.
参考文献 Reference
Elimova E et al. 2026 ASCO Gastrointestinal Cancers Symposium abstr LBA 285
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术前mFOLFIRINOX对比PAXG治疗可切除胰腺导管腺癌（1/17/2026）
Preoperative mFOLFIRINOX versus PAXG for resectable pancreatic ductal adenocarcinoma: PACT-21 CASSANDRA
方法: CASSANDRA(NCT04793932,)是一项随机, 开放标签, 2×2析因III期临床试验，涉及17家意大利学术医院。符合条件的患者年龄为18-75岁，经病理学确诊为可切除或边缘可切除的胰腺导管腺癌。研究设计采用1:1随机化，并按中心和糖类抗原19-9进行分层。参与者首先被随机分配接受PAXG（卡培他滨总日剂量为1250 mg/m2，分两次服用，每次625 mg/m2；静脉注射顺铂30 mg/m2, 纳米紫杉醇150 mg/m2和吉西他滨800 mg/m2，每14天一次）或mFOLFIRINOX（静脉注射氟尿嘧啶2400 mg/m2, 亚叶酸钙400 mg/m2, 伊立替康150 mg/m2和奥沙利铂85 mg/m2，每14天一次），疗程4个月，随后进行第二次随机化，接受术前或术后2个月的额外化疗。主要终点是意向治疗人群的无事件生存期，安全性人群包括所有接受至少一个疗程指定治疗的患者。此处报告首次随机分组的结果。该试验已完成患者招募并达到首次随机分组主要分析所需的事件数，但总生存期的随访仍在进行中。
结果 2020 年 11 月 3 日至 2024 年 4 月 24 日期间，132 名符合条件的患者被分配到 PAXG 组，128 名患者被分配到 mFOLFIRINOX 组。在 PAXG 组中，中位年龄为 65 岁（四分位距 60-70 岁），132 名患者中有 68 名（52%）为女性，64 名（48%）为男性。在 mFOLFIRINOX 组中，中位年龄为 63 岁（四分位距 57-69 岁），128 名患者中有 62 名（48%）为女性，66 名（52%）为男性。所有 260 名患者均接受了至少一次指定的化疗。与 mFOLFIRINOX 相比，PAXG 延长了中位无事件生存期（16.0 个月 [95% CI 12.4-19.8] vs 10.2 个月 [8.6-13.5]；风险比 0.63 [0.47-0.84]；p=0.0018）。PAXG 组 132 名患者中有 87 名（66%）和 mFOLFIRINOX 组 128 名患者中有 78 名（61%）出现至少一次 3 级或更严重的不良事件，其中包括一例死亡事件。
解释: 与改良FOLFIRINOX方案相比，PAXG方案显著改善了可切除或临界可切除胰腺导管腺癌患者的无事件生存期。术前PAXG方案可被视为可切除或临界可切除PDAC的标准治疗方案。
Methods: CASSANDRA (NCT04793932) is a randomized, open-label, 2×2 factorial phase III clinical trial involving 17 Italian academic hospitals. Eligible patients were 18-75 years of age with histologically confirmed resectable or borderline resectable pancreatic ductal adenocarcinoma. The study design used 1:1 randomization and was stratified by center and CA 19-9. Participants were first randomized to receive either PAXG (capecitabine total daily dose of 1250 mg/m2, given in two divided doses of 625 mg/m2 each; intravenous cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2 and gemcitabine 800 mg/m2, every 14 days) or mFOLFIRINOX (intravenous fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 and oxaliplatin 85 mg/m2, every 14 days) for 4 months, followed by a second randomization to receive an additional 2 months of chemotherapy either pre- or post-operatively. The primary endpoint was event-free survival in the intention-to-treat population, and the safety population included all patients who received at least one cycle of the assigned treatment. The results of the first randomization are reported here. The trial has completed patient recruitment and reached the number of events required for the primary analysis of the first randomization, but follow-up for overall survival is still ongoing.
Results: Between November 3, 2020, and April 24, 2024, 132 eligible patients were assigned to the PAXG group and 128 patients to the mFOLFIRINOX group. In the PAXG group, the median age was 65 years (interquartile range 60-70 years), and 68 of 132 patients (52%) were female and 64 (48%) were male. In the mFOLFIRINOX group, the median age was 63 years (interquartile range 57-69 years), with 62 out of 128 patients (48%) being female and 66 (52%) being male. All 260 patients received at least one dose of the assigned chemotherapy. Compared to mFOLFIRINOX, PAXG extended the median event-free survival (16.0 months [95% CI 12.4-19.8] vs 10.2 months [8.6-13.5]; hazard ratio 0.63 [0.47-0.84]; p=0.0018).
Eighty-seven out of 132 patients (66%) in the PAXG group and 78 out of 128 patients (61%) in the mFOLFIRINOX group experienced at least one grade 3 or higher adverse event, including one death.
Interpretation: Compared to the modified FOLFIRINOX regimen, the PAXG regimen significantly improved event-free survival in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma. Preoperative PAXG can be considered a standard treatment option for resectable or borderline resectable PDAC.
参考文献 Reference
Reni M et al. Lancet 2025 ; 406 :2945
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食品添加剂防腐剂摄入量与癌症发病率 (1/11/2026)
Intake of food additive preservatives and incidence of cancer
设计: 前瞻性队列研究。 研究地点 法国 NutriNet-Santé 队列，2009-2023 年。
参与者: 105,260 名（≥15 岁）无既往癌症病史的参与者，他们在基线时完成了至少两次 24 小时膳食记录。
主要结局指标: 累积时间依赖性防腐剂摄入量，包括工业食品品牌中的防腐剂，使用重复的 24 小时膳食记录进行评估，并通过多个成分数据库和针对最常食用的添加剂-食物组合的食品产品进行专门的实验室检测进行评估。使用多变量比例风险 Cox 模型，调整潜在混杂因素后，对三类防腐剂（如果至少三分之一的参与者摄入了防腐剂，则定义为按性别划分的三分位数；否则定义为非消费者和低于或高于按性别划分的中位数的消费者）摄入量与癌症发病率之间的关联进行表征。
结果: 参与者的平均年龄为 42.0 岁（标准差 14.5 岁），78.7% 为女性。4,226 名参与者被诊断出患有新发癌症（平均随访时间 7.57 年（标准差 4.56 年）），其中包括 1,208 例乳腺癌, 508 例前列腺癌, 352 例结直肠癌和 2,158 例其他癌症。几种防腐剂摄入量较高与癌症发病率较高相关：非抗氧化剂总量与总体癌症相关（高摄入量组与非摄入量组或低摄入量组的风险比为 1.16（95% 置信区间 1.07 至 1.26）；60 岁时的绝对癌症风险分别为 13.3% 和 12.1%）和乳腺癌（1.22（1.05 至 1.41）；5.7% 和 4.8%）；山梨酸盐总量，特别是山梨酸钾，与总体癌症相关（1.14（1.04 至 1.24）；13.4% 和 11.8%）和乳腺癌（1.26（1.07 至 1.49）；5.7% 和 4.6%）；亚硫酸盐总量与总体癌症相关（1.12（1.02 至 1.24）；13.4% 和 11.9%）；焦亚硫酸钾与总体癌症相关（1.11（1.03 至 1.20）；13.5% 和 12.0%）和乳腺癌（1.20（1.04 至 1.38）；5.7% 和 4.9%）；亚硝酸钠与前列腺癌相关（1.32（1.02 至 1.70）；4.2% 和 3.4%）；硝酸钾与总体癌症相关（1.13（1.05 至 1.23）；14.0% 和 12.0%）和乳腺癌（1.22（1.05 至 1.41）；5.9% 和 4.8%）；乙酸盐总量与总体癌症相关（1.15（1.06 至 1.25）；14.3% 和 12.2%）和乳腺癌（1.25（1.07 至 1.45）；6.1% 和 4.9%）；乙酸与总体癌症相关（1.12（1.01 至 1.25）；14.4% 和 12.4%）。此外，苯甲酸钠与总体癌症（1.12 (1.04至1.22)；13.5%，11.9%）和乳腺癌（1.21 (1.04至1.41)；5.7%，4.8%）的发生率相关。在单独研究的17种防腐剂中，有11种与癌症发病率无关。
结论：这项大型前瞻性队列研究观察到，摄入工业食品中广泛使用的防腐剂与较高的癌症发病率（总体癌症、乳腺癌和前列腺癌）之间存在多种正相关关系。需要基于健康效应生物标志物的流行病学研究和实验研究来深入了解其作用机制。如果这些新数据得到证实，则需要重新评估食品行业使用这些添加剂的相关法规，以加强消费者保护。同时，这些研究结果也支持建议消费者选择新鲜制作, 加工程度最低的食物。
Design: Prospective cohort study. Study location: NutriNet-Santé cohort, France, 2009-2023. Participants: 105,260 participants (≥15 years old) with no prior history of cancer, who completed at least two 24-hour dietary records at baseline. Main outcome measures: Cumulative time-dependent preservative intake, including preservatives in industrial food brands, assessed using repeated 24-hour dietary records and evaluated through multiple ingredient databases and dedicated laboratory testing of food products for the most frequently consumed additive-food combinations. The association between intake of three categories of preservatives (defined as tertiles by sex if at least one-third of participants consumed the preservative; otherwise defined as non-consumers and consumers below or above the median by sex) and cancer incidence was characterized using multivariate proportional hazards Cox models, adjusted for potential confounding factors.
Results: The mean age of participants was 42.0 years (standard deviation 14.5 years), and 78.7% were women. 4,226 participants were diagnosed with new-onset cancer (mean follow-up time 7.57 years (standard deviation 4.56 years)), including 1,208 cases of breast cancer, 508 cases of prostate cancer, 352 cases of colorectal cancer, and 2,158 cases of other cancers. Several preservatives were associated with a higher incidence of cancer at higher intake levels: total non-antioxidant preservatives were associated with overall cancer (risk ratio of 1.16 (95% confidence interval 1.07 to 1.26) for the high intake group compared to the non-intake or low intake group; absolute cancer risk at age 60 was 13.3% and 12.1%, respectively) and breast cancer (1.22 (1.05 to 1.41); 5.7% and 4.8%); total sorbates, particularly potassium sorbate, were associated with overall cancer (1.14 (1.04 to 1.24); 13.4% and 11.8%) and breast cancer (1.26 (1.07 to 1.49); 5.7% and 4.6%); total sulfites were associated with overall cancer (1.12 (1.02 to 1.24); 13.4% and 11.9%); potassium metabisulfite was associated with overall cancer (1.11 (1.03 to 1.20); 13.5% and 12.0%) and breast cancer (1.20 (1.04 to 1.38); 5.7% and 4.9%); sodium nitrite was associated with prostate cancer (1.32 (1.02 to 1.70); 4.2% and 3.4%); potassium nitrate was associated with overall cancer (1.13 (1.05 to 1.23); 14.0% and 12.0%) and breast cancer (1.22 (1.05 to 1.41); 5.9% and 4.8%); and total acetates were associated with overall cancer (1.15 (1.06 to 1.25); 14.3% and 12.2%) and breast cancer (1.25 (1.07 to 1.45); 6.1% and 4.9%); acetic acid was associated with overall cancer (1.12 (1.01 to 1.25); 14.4% and 12.4%). In addition, sodium benzoate was associated with overall cancer (1.12 (1.04 to 1.22); 13.5%, 11.9%) and breast cancer (1.21 (1.04 to 1.41); 5.7%, 4.8%). Of the 17 preservatives studied individually, 11 were not associated with cancer incidence.
Conclusion: This large prospective cohort study observed multiple positive associations between the intake of widely used preservatives in processed foods and higher cancer incidence (overall cancer, breast cancer, and prostate cancer). Epidemiological studies and experimental research based on health effect biomarkers are needed to gain a deeper understanding of the mechanisms involved. If these new data are confirmed, the regulations governing the use of these additives in the food industry need to be re-evaluated to strengthen consumer protection. These findings also support advising consumers to choose freshly prepared, minimally processed foods.
参考文献 Reference
Hasenböhler A. et al BMJ 2026 ; 392 : e084917
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IgG4 相关疾病患者癌症风险增加 (1/10/2026)
Increased cancer risk in patients with IgG4-related disease in South Korea
免疫球蛋白G4相关疾病（IgG4-RD）是一种慢性炎症性疾病，特征是IgG4阳性浆细胞浸润、席纹状纤维化和闭塞性静脉炎。IgG4-RD几乎可以累及任何器官系统，包括胰腺, 唾液腺, 胆道系统, 肾脏和肺部，并且通常表现为肿块样病变，对糖皮质激素治疗反应良好。本研究旨在利用全国性人群队列评估IgG4-RD患者的癌症风险。
研究者从韩国国家健康保险服务数据库中确定了2012年1月至2020年12月期间新诊断为IgG4-RD的2,150名患者。对患者进行随访，直至发生癌症、死亡或2021年12月31日。计算标准化发病率比和95%置信区间，以比较IgG4-RD患者与普通人群的癌症发病率。根据性别, 诊断年龄, 随访时间和免疫抑制剂的使用情况进行亚组分析。IgG4-RD患者的总体癌症风险显著增加（标准化发病率 4.12，95% CI 3.48–4.85），包括实体瘤（标准化发病率 3.33，95% CI 2.74–4.02）和血液系统恶性肿瘤（标准化发病率 15.31，95% CI 10.17–22.13）。在实体瘤中，胰腺癌（标准化发病率 14.54，95% CI 8.31–23.62）, 中枢神经系统癌症和胆道癌的风险最高。骨髓增生异常综合征和非霍奇金淋巴瘤是最常见的血液系统恶性肿瘤。女性患者的癌症风险更高。风险在IgG4-RD诊断后的第一年达到峰值（标准化发病率 7.13，95% CI 5.65–8.89）。
IgG4-RD患者发生癌症的风险显著升高，特别是骨髓增生异常综合征, 非霍奇金淋巴瘤, 胰腺癌和胆道癌。因此，有必要对IgG4-RD患者进行密切的恶性肿瘤监测，尤其是在诊断后的第一年。
Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by IgG4-positive plasma cell infiltration, storiform fibrosis, and obliterative phlebitis. IgG4-RD can affect almost any organ system, including the pancreas, salivary glands, biliary system, kidneys, and lungs, and typically presents as mass-like lesions that respond well to corticosteroid treatment. This study aimed to assess the cancer risk in patients with IgG4-RD using a nationwide population cohort.
Researchers identified 2,150 patients newly diagnosed with IgG4-RD between January 2012 and December 2020 from the South Korean National Health Insurance Service database. Patients were followed until cancer development, death, or December 31, 2021. Standardized incidence ratios and 95% confidence intervals were calculated to compare cancer incidence in IgG4-RD patients with that of the general population. Subgroup analyses were performed based on sex, age at diagnosis, follow-up time, and immunosuppressant use.
The overall cancer risk was significantly increased in IgG4-RD patients (standardized incidence ratio 4.12, 95% CI 3.48–4.85), including solid tumors (standardized incidence ratio 3.33, 95% CI 2.74–4.02) and hematological malignancies (standardized incidence ratio 15.31, 95% CI 10.17–22.13). Among solid tumors, pancreatic cancer (standardized incidence ratio 14.54, 95% CI 8.31–23.62), central nervous system cancer, and biliary tract cancer had the highest risks. Myelodysplastic syndrome and non-Hodgkin lymphoma were the most common hematological malignancies. Female patients had a higher risk of cancer. The risk peaked in the first year after IgG4-RD diagnosis (standardized incidence ratio 7.13, 95% CI 5.65–8.89).
Patients with IgG4-related disease (IgG4-RD) have a significantly increased risk of developing cancer, particularly myelodysplastic syndrome, non-Hodgkin lymphoma, pancreatic cancer, and biliary tract cancer. Therefore, close monitoring for malignancies is necessary in patients with IgG4-RD, especially during the first year after diagnosis.
参考文献 Reference
So H. et al. Scientific Reports 2025; 15 Article number 37273
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比较 giredestrant 与标准内分泌疗法作为ER阳性/HER2 阴性早期乳腺癌辅助治疗 (1/4/2026)
Adjuvant therapy using giredestrant vs standard-of-care for ER-positive, HER2-negative early breast cancer: lidERA trial
这项全球性, 随机, 开放标签, 多中心试验招募了 I 期至 III 期激素受体 (ER) 阳性, HER2 阴性乳腺癌患者，以评估giredestrant与现有标准治疗方案相比的安全性和有效性。参与者的中位年龄为 54 岁，其中 59% 为绝经后女性。4,170 名患者按 1:1 的比例随机分配，分别接受 30 mg giredestrant或四种标准内分泌疗法之一（由处方医生自行选择他莫昔芬, 来曲唑, 阿那曲唑或依西美坦)。患者每天接受治疗，直至治疗满 5 年或出现不可耐受的毒性反应。 患者的主要终点为无侵袭性疾病生存期；次要终点包括总生存期和无远处复发间隔。
结果: 该试验在预先设定的中期分析中达到了主要终点。中位随访时间为 32.3 个月后，接受giredestrant治疗的患者的无侵袭性疾病生存期显著优于接受标准内分泌治疗的患者，且在随访期间发生侵袭性疾病进展的可能性降低了 30%。 次要终点无远处复发间隔也达到了预设目标, 比标准治疗组的患者低 31%。由于随访时间有限，总生存期数据尚不成熟。
在giredestrant和标准治疗组中 ，最常见的治疗相关不良事件是关节痛、潮热和头痛（所有这些事件主要为轻度且不严重），且两组的发生率相似。3级和4级治疗相关不良事件包括高血压和关节痛。心动过缓是口服选择性雌激素受体降解剂（SERD）的已知类效应， giredestrant的心动过缓发生率为11.3%，高于标准治疗组的3.2%。大多数病例为1级，无症状且不严重，无需中断/停止治疗。2级不良事件（<1%）受到合并症/降压药的影响，所有病例均已痊愈。Giredestrant组因治疗相关不良事件导致治疗中断的发生率为5.3%，低于标准内分泌治疗组的8.2%。
lidERA研究结果表明，giredestrant在临床上优于他莫昔芬和芳香化酶抑制剂，使giredestrant有望成为早期激素受体阳性, HER2阴性乳腺癌患者内分泌治疗的新标准。
This global, randomized, open-label, multicenter trial enrolled patients with stage I to III hormone receptor (ER)-positive, HER2-negative breast cancer to evaluate the safety and efficacy of giredestrant compared to existing standard treatment regimens. The median age of participants was 54 years, with 59% being postmenopausal women. A total of 4,170 patients were randomly assigned in a 1:1 ratio to receive either 30 mg of giredestrant or one of four standard endocrine therapies (tamoxifen, letrozole, anastrozole, or exemestane, chosen by the treating physicians). Patients received treatment daily until 5 years of treatment were completed or until intolerable toxicity. The primary endpoint was invasive disease-free survival; secondary endpoints included overall survival and distant recurrence-free interval.
Results: The trial met its primary endpoint in a pre-specified interim analysis. After a median follow-up of 32.3 months, patients treated with giredestrant had significantly better invasive disease-free survival than those receiving standard endocrine therapy, with a 30% lower likelihood of invasive disease progression during the follow-up period. The secondary endpoint of distant recurrence-free interval also met its pre-specified target, being 31% lower than in the standard treatment group. Overall survival data were not yet mature due to the limited follow-up time.
In both the giredestrant and standard treatment groups, the most common treatment-related adverse events were arthralgia, hot flashes, and headache (primarily mild), with similar incidence rates in both groups. Grade 3 and 4 treatment-related adverse events included hypertension and arthralgia. Bradycardia, a known class effect of oral selective estrogen receptor degraders (SERDs), occurred in 11.3% of patients treated with giredestrant, compared to 3.2% in the standard treatment group. Most cases were grade 1, asymptomatic, and not serious, requiring no treatment interruption/discontinuation. Grade 2 adverse events (<1%) were influenced by comorbidities/antihypertensive medications, and all cases resolved. In the giredestrant group, the incidence of treatment discontinuation due to treatment-related adverse events was 5.3%, which was lower than the 8.2% in the standard endocrine therapy group.
The lidERA study results indicate that giredestrant is clinically superior to tamoxifen and aromatase inhibitors, suggesting that giredestrant would be considered a new standard of endocrine therapy for patients with early-stage hormone receptor-positive, HER2-negative breast cancer.
参考文献 Reference
Bardia A et al. 2025 San Antonio Breast Cancer Symp (SABCS) Abstr GS1-10
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Botensilimab 联合巴斯蒂利单抗联合 balstilimab 治疗难治性卵巢癌患者 (1/3/2026)
Botensilimab plus balstilimab for refractory ovarian cancer
这是一项Ib期临床研究旨在评估Botensilimab（一种Fc片段增强型抗细胞毒性T淋巴细胞相关抗原4 (CTLA-4抗体，其作用机制与第一代CTLA-4抑制剂不同）联合巴斯替利单抗（抗程序性细胞死亡蛋白1抗体）在难治性卵巢癌患者扩展队列中的安全性和有效性。
方法: Botensilimab以1 mg/kg或2 mg/kg的剂量每6周静脉注射一次，联balstilimabL以3 mg/kg的剂量每2周静脉注射一次（最长2年）。主要研究目标是评估安全性和耐受性。疗效终点包括根据实体瘤疗效评价标准评 估的客观响应率, 响应持续时间和无进展生存期。总生存期为探索性终点。
结果: 共有44例患者可进行安全性评估（既往接受过中位3线治疗；中位随访时间9.6个月（范围0.6-36.6个月）），35例患者可进行疗效评估。最常见的治疗相关不良事件是腹泻/结肠炎（43%；16%为3级），未发生治疗相关死亡。
经RECIST确认的客观响应率为23%（8/35；95% CI 10%至40%；1例完全响应，7例部分响应，临床获益率（完全响应, 部分响应或疾病稳定≥24周）为31%（11/35；95% CI 17%至49%）。中位响应持续时间为 9.7 个月（95% CI 2.8 至未达到），中位无进展生存期为 2.8 个月（95% CI 1.4 至 5.5），中位总生存期为 14.8 个月（95% CI 12.1 至未达到），12 个月总生存率为 75%（95% CI 55% 至 86%）。
免疫表型分析和生物标志物数据显示，应答患者的 FcγRIIIA+CD11c+ 细胞数量显著更高，程序性死亡配体 1 的表达也更高；T 细胞浸润的肿瘤与临床获益之间存在强相关性；不同组织学亚型之间的免疫结构也存在差异。
结论：Botensilimab/balstilimab 联合疗法在目前尚无标准治疗方案的难治性卵巢癌患者中显示出深度且持久的响应和完全响应。RECIST 标准低估了临床获益，有 11 例患者实现了持续时间≥ 24 周的长期/具有临床意义的疾病稳定。毒性反应 可控且可逆。Botensilimab/balstilimab 联合疗法在既往接受过多种治疗的患者中展现出令人鼓舞的临床疗效，值得进一步研究。
This is a phase Ib clinical study designed to evaluate the safety and efficacy of botensilimab (an Fc-enhanced anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4 antibody with a different mechanism of action than the first-generation CTLA-4 inhibitors) in combination with balstilimab (an anti-programmed cell death protein 1 antibody) in an expanded cohort of patients with refractory ovarian cancer.
Methods: Botensilimab was administered intravenously at a dose of 1 mg/kg or 2 mg/kg every 6 weeks, in combination with balstilimab administered intravenously at a dose of 3 mg/kg every 2 weeks (for up to 2 years). The primary objective was to assess safety and tolerability. Efficacy endpoints included objective response rate, duration of response, and progression-free survival as assessed by the Response Evaluation Criteria in Solid Tumors. Overall survival was an exploratory endpoint.
Results: A total of 44 patients were evaluable for safety (median of 3 prior lines of therapy; median follow-up time of 9.6 months (range 0.6-36.6 months)), and 35 patients were evaluable for efficacy. The most common treatment-related adverse event was diarrhea/colitis (43%; 16% were grade 3), and no treatment-related deaths occurred. The objective response rate confirmed by RECIST was 23% (8/35; 95% CI 10% to 40%; 1 complete response, 7 partial responses), and the clinical benefit rate (complete response, partial response, or stable disease ≥24 weeks) was 31% (11/35; 95% CI 17% to 49%). The median duration of response was 9.7 months (95% CI 2.8 to not reached), the median progression-free survival was 2.8 months (95% CI 1.4 to 5.5), and the median overall survival was 14.8 months (95% CI 12.1 to not reached), with a 12-month overall survival rate of 75% (95% CI 55% to 86%).
Immunophenotyping and biomarker data showed that responding patients had significantly higher numbers of FcγRIIIA+CD11c+ cells and higher expression of programmed death-ligand 1; a strong correlation existed between T-cell infiltration in tumors and clinical benefit; and differences in immune architecture were observed between different histological subtypes.
Conclusion: The botensilimab/balstilimab combination therapy demonstrated deep and durable responses and complete responses in patients with refractory ovarian cancer for whom no standard treatment options currently exist. The RECIST criteria underestimated the clinical benefit, with 11 patients achieving long-term/clinically meaningful disease stabilization lasting ≥ 24 weeks. Toxicities were manageable and reversible. The botensilimab/balstilimab combination therapy showed encouraging clinical efficacy in heavily pretreated patients and warrants further investigation.
参考文献 Reference
Porter R et al. J ImmunoTherapy Cancer 2025 ; Dec 23.