Luís Felipe Leite da Silva, Erick Figueiredo Saldanha, Lucas Diniz da Conceição, Mariana Macambira Noronha, Marcos Vinícius Martins Grangeiro da Silva, Renata D 'Alpino Peixoto
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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.</p><p><strong>Methods: </strong>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<sup>2</sup>.</p><p><strong>Results: </strong>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<sup>2</sup> = 60%). Common grade 3 or higher treatment-related adverse events included neutropenia (22.8%) and rash (14.9%).</p><p><strong>Conclusion: </strong>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. 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Inter-study heterogeneity was assessed using the I<sup>2</sup>.</p><p><strong>Results: </strong>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<sup>2</sup> = 60%). 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引用次数: 0
摘要
背景：转移性结直肠癌（mCRC）仍然是一个重大的临床挑战。虽然抗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，这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恢复对抗egfr药物的敏感性，这表明再挑战策略有潜在的益处。我们的研究旨在进行系统回顾和荟萃分析，以全面评估EGFR再挑战在mCRC患者中的有效性和安全性。方法：在2023年10月28日至12月24日期间，对MEDLINE、EMBASE和Cochrane数据库进行了系统检索，以确定将帕尼单抗或西妥昔单抗作为再挑战策略的临床试验。采用随机效应模型计算合并比例或风险比（HR）。使用I2评估研究间异质性。结果：在检索到的2105篇文献中，有13篇符合预定的纳入标准。其中12项为II期研究，占患者总数的92.3%。西妥昔单抗用于302例患者（75.1%），而帕尼单抗用于100例患者（24.9%）。8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）。中位无进展生存期估计为3.5个月（95% CI 2.68-6.69），中位OS为9.8个月（95% CI 6.71-12.89）。在循环肿瘤DNA （ctDNA）分析中显示RAS野生型状态的患者从抗egfr再挑战中获得了更大的益处(HR: 0.41；95% ci 0.28-0.60, i2 = 60%)。常见的3级或更高级别治疗相关不良事件包括中性粒细胞减少（22.8%）和皮疹（14.9%）。结论：这项荟萃分析强调了抗egfr再挑战作为一种有希望的治疗方法对一部分mCRC患者的有效性和安全性。观察到的野生型RAS状态（通过ctDNA分析确定）与改善的OS之间的相关性标志着精确肿瘤学指导治疗决策的前景。
Anti-EGFR Rechallenge in Metastatic Colorectal Cancer and the Role of ctDNA: A Systematic Review and Meta-analysis.
Background: 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.
Methods: 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 I2.
Results: 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, I2 = 60%). Common grade 3 or higher treatment-related adverse events included neutropenia (22.8%) and rash (14.9%).
Conclusion: 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.
期刊介绍：
The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.
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