Anti-EGFR retreatment in RAS/BRAF wild-type mCRC

In this video, Dr Vittorio Studiale and Dr Gertjan Rasschaert discuss an individual patient data pooled analysis of five randomised clinical trials, presented at ESMO GI 2026 in Munich.¹ The analysis addressed a pragmatic clinical question in patients with pMMR/MSS, RAS/BRAF wild-type metastatic colorectal cancer (mCRC) who had progressed after first-line anti-EGFR-based therapy. Although treatment guidelines generally recommend switching both the chemotherapy backbone and the biological agent after progression, anti-EGFR retreatment is sometimes considered in clinical practice, particularly after a treatment holiday or secondary surgery. 

The pooled cohort included patients who had received first-line chemotherapy plus anti-EGFR therapy and subsequently received either retreatment with the same chemotherapy backbone plus anti-EGFR therapy or a switch to a different chemotherapy backbone plus anti-VEGF/VEGFR therapy. Overall, objective response rate and progression-free survival were similar between the two strategies. However, the anti-EGFR-free interval appeared to be relevant: patients with an interval of at least 4 months derived more benefit from anti-EGFR retreatment in terms of response and progression-free survival, whereas patients with a shorter interval appeared to benefit more from switching strategy. 

Overall survival was longer with anti-EGFR retreatment than with the switch strategy, and this finding remained consistent after propensity score matching. Dr Studiale notes that these overall survival data should be interpreted cautiously because of the retrospective nature of the analysis, baseline imbalances and the potential influence of subsequent treatment lines. 

The discussion also highlights the future role of molecular selection. While these pragmatic data may help guide treatment sequencing when ctDNA testing is not available, prospective studies incorporating ctDNA are needed to refine patient selection and optimise retreatment strategies.