Anti-EGFR rechallenge compared with standard of care for patients with ctDNA RAS/BRAF wild-type chemorefractory metastatic colorectal cancer: A systematic review and meta-analysis.

Anti-EGFR rechallenge emerged as a potential therapeutic option for patients with chemorefractory metastatic colorectal cancer (mCRC) that maintained a circulating tumor DNA (ctDNA) RAS/BRAF wild type (WT) status. However, its efficacy compared to standard of care (SoC) in randomized controlled trials (RCTs) remains uncertain. In our systematic review and meta-analysis, we investigated the outcomes of anti-EGFR rechallenge versus SoC for patients with pretreated ctDNA RAS/BRAF WT mCRC. This study followed the PRISMA guidelines, and a systematic search of PubMed and ASCO/ESMO meeting abstracts was conducted in October 2025 for relevant RCTs. Pooled odds ratios (OR) for disease control rate (DCR) and objective response rate (ORR), and hazard ratios (HR) for survival outcomes were calculated. We identified three phase II randomized trials with 320 patients. Anti-EGFR rechallenge significantly improved DCR (OR = 3.39, 95 % CI 2.13-5.39), ORR (OR = 5.13, 95 % CI 2.30-11.41) and progression free survival (HR 0.674; 95 % CI, 0.499-0.909; p = 0.009) compared to SoC. No overall survival benefit was detected (HR 0.895; 95 % CI 0.736-1.087; p = 0.263). These findings support the use of anti-EGFR rechallenge strategy aslater-line treatment when tumor shrinkage is a clinical priority. Further evidence from prospective trials is required.