da Silva Luís Felipe Leite, Saldanha Erick Figueiredo, da Conceição Lucas Diniz, Noronha Mariana Macambira, da Silva Marcos Vinícius Martins Grangeiro, Peixoto Renata D 'Alpino
Universidade Federal Fluminense, Niterói, RJ, Brazil.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
J Gastrointest Cancer. 2024 Dec 3;56(1):28. doi: 10.1007/s12029-024-01152-1.
Metastatic colorectal cancer (mCRC) remains a significant clinical challenge. While anti-EGFR inhibitors have improved survival rates, their long-term efficacy is limited by disease progression, which is often associated with the development of acquired resistance mutations. However, some patients may regain sensitivity to anti-EGFR agents after alternative therapies, suggesting a potential benefit for rechallenge strategies. Our study aims to conduct a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of EGFR rechallenge in patients with mCRC.
A systematic search of the MEDLINE, EMBASE, and Cochrane databases was conducted between October 28 and December 24, 2023, to identify clinical trials investigating treatment regimens incorporating panitumumab or cetuximab as a rechallenge strategy. Pooled proportions or hazard ratios (HR) were calculated using a random effects model. Inter-study heterogeneity was assessed using the I.
Among the 2105 articles identified through the search, 13 met the predetermined inclusion criteria. Of these, 12 were phase II studies, encompassing 92.3% of the patient population. Cetuximab was administered to 302 patients (75.1%), whereas panitumumab was utilized in 100 patients (24.9%).A pooled analysis of eight studies demonstrated an objective response rate of 20.50% (95% CI 7.94 to 33.07) and a disease control rate of 67.35% (95% CI 58.60 to 76.09). The median progression-free survival was estimated at 3.5 months (95% CI 2.68-6.69), with a median OS of 9.8 months (95% CI 6.71-12.89). Patients exhibiting RAS wild-type status in circulating tumor DNA (ctDNA) analysis derived enhanced benefits from anti-EGFR rechallenge (HR: 0.41; 95% CI 0.28-0.60, I = 60%). Common grade 3 or higher treatment-related adverse events included neutropenia (22.8%) and rash (14.9%).
This meta-analysis underscores the efficacy and safety of anti-EGFR rechallenge as a promising therapeutic approach for a subset of patients afflicted with mCRC. The observed correlation between wild-type RAS status, as determined through ctDNA analysis, and improved OS signals the prospect of precision oncology in guiding treatment decisions.
转移性结直肠癌（mCRC）仍然是一项重大的临床挑战。虽然抗表皮生长因子受体（EGFR）抑制剂提高了生存率，但其长期疗效受到疾病进展的限制，而疾病进展通常与获得性耐药突变的发生有关。然而，一些患者在接受替代治疗后可能会重新对抗EGFR药物敏感，这表明再次挑战策略可能有益。我们的研究旨在进行系统评价和荟萃分析，以全面评估EGFR再次挑战对mCRC患者的疗效和安全性。
于2023年10月28日至12月24日对MEDLINE、EMBASE和Cochrane数据库进行系统检索，以确定研究将帕尼单抗或西妥昔单抗作为再次挑战策略的治疗方案的临床试验。使用随机效应模型计算合并比例或风险比（HR）。使用I统计量评估研究间的异质性。
在通过检索确定的2105篇文章中，13篇符合预定的纳入标准。其中，12项为II期研究，涵盖了92.3%的患者群体。302例患者（75.1%）接受了西妥昔单抗治疗，而100例患者（24.9%）使用了帕尼单抗。八项研究的汇总分析显示，客观缓解率为20.50%（95%CI 7.94至33.07），疾病控制率为67.35%（95%CI 58.60至76.09）。无进展生存期的中位数估计为3.5个月（95%CI 2.68 - 6.69），总生存期的中位数为9.8个月（95%CI 6.71 - 12.89）。在循环肿瘤DNA（ctDNA）分析中表现出RAS野生型状态的患者从抗EGFR再次挑战中获益更多（HR：0.41；95%CI 0.28 - 0.60，I² = 60%）。常见的3级或更高等级的治疗相关不良事件包括中性粒细胞减少（22.8%）和皮疹（14.9%）。
这项荟萃分析强调了抗EGFR再次挑战作为一种有前景的治疗方法对一部分mCRC患者的疗效和安全性。通过ctDNA分析确定的野生型RAS状态与改善的总生存期之间的观察到的相关性表明了精准肿瘤学在指导治疗决策方面的前景。
