Zhao Wensi, Chen Yongshun
Department of Oncology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, China.
Present address: Cancer Center, The Eighth Affiliated Hospital, Sun Yat-sen University Shenzhen 518033, Guangdong, China.
Am J Cancer Res. 2024 Nov 15;14(11):5378-5388. doi: 10.62347/KAFY8529. eCollection 2024.
Immune checkpoint inhibitor (ICI) has changed the situation of anti-tumor therapy. Several phase I/II clinical trials explored ICI-based combinations in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with mixed outcomes. However, real-world data regarding ICI-based combinations in this population is lacking. This retrospective study aimed to evaluate the efficacy and safety of ICI in MSS mCRC patients in third-line or above setting. A total of 143 eligible patients who received third-line or above ICI monotherapy or ICI-based combinations at the Cancer Center of Renmin Hospital of Wuhan University from June 2019 to April 2024 were included in this study. The primary endpoints were real-world median progression-free survival (PFS) and overall survival (OS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), safety and prognostic analyses. Results showed that the median PFS was 4.6 months, and the median OS was 11.8 months, with an ORR of 11.2% and a DCR of 72.7%. ICI plus small molecule tyrosine kinase inhibitors have become the most popular combination for MSS mCRC patients at third-line or above setting with a median PFS of 4.4 months and OS of 10.1 months. The subgroup of patients with liver metastasis had worse clinical outcomes and liver metastasis was an independent prognostic factor for PFS (HR = 2.35, 95% CI, 1.54-3.59; = 0.000) and OS (HR = 1.77, 95% CI, 1.06-2.96; = 0.030). Forty-eight patients received cross-line ICI and obtained significantly improved OS (15.8 months vs 10.2 months; HR = 0.59, 95% CI, 0.38-0.89; = 0.017). No new safety concerns were detected. Grade 3/4 treatment-related adverse events were generally controllable, with an incidence of 39.9%. To conclude, ICI-based combinations provide survival benefits for these heavily pretreated MSS mCRC patients with manageable safety, which is worthy of further study.
免疫检查点抑制剂（ICI）改变了抗肿瘤治疗的局面。多项I/II期临床试验探索了基于ICI的联合疗法在微卫星稳定（MSS）转移性结直肠癌（mCRC）中的应用，结果不一。然而，关于该人群中基于ICI的联合疗法的真实世界数据尚缺乏。这项回顾性研究旨在评估ICI在三线及以上治疗的MSS mCRC患者中的疗效和安全性。本研究纳入了2019年6月至2024年4月期间在武汉大学人民医院癌症中心接受三线及以上ICI单药治疗或基于ICI的联合疗法的143例符合条件的患者。主要终点是真实世界的无进展生存期（PFS）和总生存期（OS），次要终点包括客观缓解率（ORR）、疾病控制率（DCR）、安全性和预后分析。结果显示，中位PFS为4.6个月，中位OS为11.8个月，ORR为11.2%，DCR为72.7%。ICI联合小分子酪氨酸激酶抑制剂已成为三线及以上治疗的MSS mCRC患者最常用的联合方案，中位PFS为4.4个月，OS为10.1个月。肝转移患者亚组的临床结局较差，肝转移是PFS（HR = 2.35，95%CI，1.54 - 3.59；P = 0.000）和OS（HR = 1.77，95%CI，1.06 - 2.96；P = 0.030）的独立预后因素。48例患者接受了跨线ICI治疗，OS显著改善（15.8个月对10.2个月；HR = 0.59，95%CI，0.38 - 0.89；P = 0.017）。未发现新的安全问题。3/4级治疗相关不良事件总体可控，发生率为39.9%。总之，基于ICI的联合疗法为这些经过大量预处理的MSS mCRC患者带来了生存益处，安全性可控，值得进一步研究。
