Anti-EGFR rechallenge improves response and PFS but not OS in ctDNA wild-type chemorefractory mCRC

This systematic review and meta-analysis pooled data from three phase II randomized trials involving 320 patients with pretreated, chemorefractory metastatic colorectal cancer (mCRC) who had ctDNA-confirmed RAS/BRAF wild-type status. The analysis compared anti-EGFR rechallenge therapy against standard of care (SoC) in this later-line setting. The primary outcome was not reported; secondary outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Anti-EGFR rechallenge demonstrated significant improvements in several efficacy endpoints. For DCR, the odds ratio was 3.39 (95% CI 2.13-5.39), favoring rechallenge. For ORR, the odds ratio was 5.13 (95% CI 2.30-11.41). Progression-free survival also showed significant improvement with a hazard ratio of 0.674 (95% CI 0.499-0.909; p = 0.009). However, no overall survival benefit was detected (HR 0.895, 95% CI 0.736-1.087; p = 0.263). Absolute numbers for these outcomes were not reported.

Safety and tolerability data were not reported in this meta-analysis. The key limitation is that these findings are derived from a meta-analysis of only three phase II trials, and the authors explicitly state that further evidence from prospective trials is required. The practice relevance is restrained: these findings support considering anti-EGFR rechallenge as a later-line treatment option when tumor shrinkage is a clinical priority, but the lack of OS benefit and the phase II evidence base warrant caution.