Combination of anti-epidermal growth factor receptor antibodies plus trifluridine-tipiracil as rechallenge strategy improves treatment outcomes in patients with RAS/BRAF wild-type refractory metastatic colorectal cancer

Trifluridine/tipiracil (FTD-TPI) plus bevacizumab is an established option for refractory metastatic colorectal cancer (mCRC). Rechallenging RAS/BRAF-wild-type tumours with an anti-EGFR antibody in combination with FTD-TPI is emerging, yet the two strategies have not been directly compared. We retrospectively identified consecutive RAS/BRAF-wild-type, chemotherapy-refractory mCRC patients treated at National Taiwan University Hospital between December 2018 and March 2023. All had received first-line anti-EGFR therapy; subsequent treatment comprised FTD-TPI with either anti-EGFR rechallenge (n = 20) or an anti-VEGF agent (n = 10). Anti-EGFR rechallenge yielded a higher objective response rate (30% vs 0%; P = 0.074) and disease-control rate (70% vs 30%; P = 0.440), plus numerically longer median progression-free (3.4 vs 2.3 months; P = 0.524) and overall survival (12.7 vs 9.9 months; P = 0.644). After adjustment for age, sex, tumour sidedness and time from metastatic diagnosis to FTD-TPI, anti-EGFR therapy remained the only independent predictor of response (posterior OR ≈ 7; 95% credible interval 1.1-66). These data suggest that FTD-TPI plus anti-EGFR rechallenge provides greater tumour shrinkage and at least comparable survival versus FTD-TPI plus anti-VEGF in heavily pre-treated, wild-type mCRC, supporting further prospective evaluation.