Wang Yanrong, Jia Ru, Si Haiyan, Ma Yue, Fan Mengjiao, Zhang Nan, Liu Fangfang, Shi Yue, Jia Yushan, Zhang Yaoyue, Han Quanli, Wang Zhikuan, Dai Guanghai
Medical School of Chinese PLA, Beijing, China.
Department of Medical Oncology, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.
BMC Cancer. 2025 Mar 7;25(1):422. doi: 10.1186/s12885-025-13794-w.
This research aimed to assess the efficacy and safety of combining sintilimab with bevacizumab, oxaliplatin, and capecitabine as a primary therapy for patients with RAS-mutated, microsatellite stable (MSS), and metastatic colorectal cancer (mCRC).
In this prospective, open-label, single-arm, phase II trial, eligible patients received up to 8 cycles of capecitabine and oxaliplatin/bevacizumab plus sintilimab, followed by maintenance therapy with capecitabine, bevacizumab, and sintilimab every three weeks until disease progression. Treatment response was evaluated every 2 cycles (6 weeks) according to the Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint was ORR, while the secondary endpoints included PFS and AEs.
The efficacy analysis and safety analysis included 33 patients. The overall response rate was 72.7%, and the median PFS in the full analysis set was 12.9 months (95% CI: 7.5-18.3), and median OS was not reached. Patients with liver metastases demonstrated a higher ORR (20/24 [83.3%]) than those without (4/9 [44.4%], p = 0.073), and the median PFS was 14.7 for patients with liver metastases and 9.6 months for those without (HR: 1.05, 95%CI: 0.34-3.24; p = 0.932). Most immune-related AEs had grades 1-2, and immunotherapy was discontinued in 4 patients due to immune-related AEs. No treatment-related deaths occurred during the study.
The therapeutic regimen showed encouraging antitumor effects and a favorable safety profile in patients with RAS mutations, MSS, and mCRC, yielding durable results throughout an extended follow-up duration, irrespective of the presence of liver metastases. This research is of great significance because it addresses the limited treatment options in the field of MSS mCRC patients. By providing new treatment strategies or methods, it brings more hope and choices to patients and offers valuable new insights and research directions to the medical community.
ClinicalTrials.gov: NCT06206096. Registered on May 26, 2021.
本研究旨在评估将信迪利单抗与贝伐珠单抗、奥沙利铂和卡培他滨联合作为RAS突变、微卫星稳定（MSS）的转移性结直肠癌（mCRC）患者一线治疗的疗效和安全性。
在这项前瞻性、开放标签、单臂、II期试验中，符合条件的患者接受最多8个周期的卡培他滨和奥沙利铂/贝伐珠单抗加信迪利单抗治疗，随后每三周接受卡培他滨、贝伐珠单抗和信迪利单抗维持治疗，直至疾病进展。根据实体瘤疗效评价标准1.1版每2个周期（6周）评估一次治疗反应。主要终点为客观缓解率（ORR），次要终点包括无进展生存期（PFS）和不良事件（AE）。
疗效分析和安全性分析纳入33例患者。总缓解率为72.7%，全分析集的中位PFS为12.9个月（95%CI：7.5 - 18.3），中位总生存期（OS）未达到。有肝转移的患者ORR更高（20/24 [83.3%]）高于无肝转移的患者（4/9 [44.4%]，p = 0.073），有肝转移患者的中位PFS为14.7个月，无肝转移患者为9.6个月（风险比[HR]：1.05，95%CI：0.34 - 3.24；p = 0.932）。大多数免疫相关AE为1 - 2级，4例患者因免疫相关AE停用免疫治疗。研究期间未发生与治疗相关的死亡。
该治疗方案在RAS突变、MSS和mCRC患者中显示出令人鼓舞的抗肿瘤效果和良好的安全性，在延长的随访期内产生了持久的结果，无论是否存在肝转移。本研究具有重要意义，因为它解决了MSS mCRC患者领域治疗选择有限的问题。通过提供新的治疗策略或方法，为患者带来了更多希望和选择，并为医学界提供了有价值的新见解和研究方向。
ClinicalTrials.gov：NCT06206096。于2021年5月26日注册。
