Wang Peng-Jian, Wang Jing, Yao Xue-Min, Cheng Wei-Li, Sun Lu, Yan Jie, Yu Yong-Ling, Li Su-Yao, Li Da-Peng, Jia Jing-Hao
Clinical Medical School, North China University of Science and Technology, Tangshan 063000, Hebei Province, China.
Department of Radiochemotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei Province, China.
World J Gastrointest Oncol. 2025 May 15;17(5):105027. doi: 10.4251/wjgo.v17.i5.105027.
BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and deadly cancers globally, particularly in China. Treatment challenges remain in advanced and metastatic cases, especially in third- and fourth-line settings. The combination of targeted therapies with immune checkpoint inhibitors (ICIs) has shown potential in addressing the limitations of single-agent treatments. AIM: To evaluate the efficacy and safety of targeted therapy (TT) alone and in combination with ICIs for metastatic CRC (mCRC). METHODS: A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC. A total of 99 patients treated with regorafenib or fruquintinib, with or without ICIs, were enrolled. Propensity score matching (PSM) and inverse probability weighting (IPW) were employed to balance baseline characteristics. The primary endpoint was progression-free survival (PFS), while overall survival (OS) and safety were secondary. RESULTS: Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses (original: 6.0 3.4 months, < 0.01; PSM: 6.15 4.25 months, < 0.05; IPW: 5.6 3.3 months, < 0.01). Although the median OS showed a trend toward improvement in the combination group, the difference was insignificant. Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression (hazard ratio = 0.38, < 0.001). Adverse events (AEs) were generally manageable with both regimens, while serious AEs (grade 3-4) were primarily hypertension, fatigue, and reduced platelet counts. All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug, and no treatment-related deaths were observed. CONCLUSION: The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC, accompanied by a favorable safety profile. These findings underscore the benefits of combination therapy in this setting, warranting further investigation in larger prospective clinical trials.
背景：结直肠癌（CRC）是全球最常见且致命的癌症之一，在中国尤为如此。晚期和转移性病例的治疗仍面临挑战，特别是在三线和四线治疗中。靶向治疗与免疫检查点抑制剂（ICI）联合使用已显示出解决单药治疗局限性的潜力。 目的：评估单独使用靶向治疗（TT）以及与ICI联合用于转移性结直肠癌（mCRC）的疗效和安全性。 方法：进行了一项多中心回顾性观察研究，以评估单独使用TT以及与ICI联合用于mCRC的疗效和安全性。共纳入99例接受瑞戈非尼或呋喹替尼治疗的患者，无论是否使用ICI。采用倾向评分匹配（PSM）和逆概率加权（IPW）来平衡基线特征。主要终点是无进展生存期（PFS），总生存期（OS）和安全性为次要终点。 结果：在所有分析中，接受联合治疗的患者的中位PFS率明显长于接受TT治疗的患者（原始数据：6.0对3.4个月，P<0.01；PSM：6.15对4.25个月，P<0.05；IPW：5.6对3.3个月，P<0.01）。虽然联合组的中位OS显示出改善趋势，但差异不显著。Cox回归分析显示，TT与ICI联合使用显著降低了疾病进展风险（风险比=0.38，P<0.001）。两种治疗方案的不良事件（AE）通常均可管理，而严重AE（3-4级）主要为高血压、疲劳和血小板计数降低。所有AE均通过对症治疗或停药得到有效控制，未观察到与治疗相关的死亡。 结论：对于晚期mCRC患者，TT与ICI联合使用在PFS方面具有显著优势，且安全性良好。这些发现强调了联合治疗在这种情况下的益处，值得在更大规模的前瞻性临床试验中进一步研究。
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