What is the optimal treatment strategy of salvage line treatment after progression on anti-epidermal growth factor receptor monoclonal antibody in patients with tissue <i>RAS/BRAF</i> wild-type metastatic colorectal cancer?

138 Background: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) and anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) re-challenge are treatment options for tissue RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) in salvage line, although the optimal treatment sequence of salvage line remains unclear. Methods: RAS/BRAF WT mCRC patients refractory to anti-EGFR mAb were retrospectively enrolled at a single cancer institute from November 2017 to April 2024. We compared responses, progression-free survival (PFS), and overall survival (OS) between Group A (anti-EGFR mAb re-challenge given first) and B (FTD/TPI plus BEV given first). We compared responses between Group C (treated with anti-EGFR mAb re-challenge at any line) and D (treated with FTD/TPI plus BEV at any line). We explored the clinical factors related to the treatment efficacy using multivariate analysis. Results: A total of 89 patients (median age, 63 years) were included. The cohort included 74 patients with a primary lesion in the left-sided colon, while 15 patients had a primary lesion in the right-sided colon. The response rate (RR) was 3.4%. The disease control rate (DCR) was 52.8%. The median PFS (mPFS) and OS (mOS) were 3.5 months (95% confidence interval [CI], 2.8-4.2) and 12.8 months (95% CI, 8.8-15.7) respectively. Two of 18 patients (11.1%) in Group A and 1 of 71 patients (1.4%) in Group B achieved partial response (PR). The RR of Group C was significantly higher than Group D (9.6% vs 1.2%; p = 0.031). Both PFS and OS showed no significant difference between Group A and B (mPFS: 3.3 vs 3.9 months; hazard ratio [HR], 1.08; 95% CI, 0.63-1.84; p = 0.79) (mOS: 12.8 vs 15.0 months; HR, 0.90; 95% CI, 0.49-1.65; p = 0.72). Multivariate analysis identified that primary tumor resection was associated with PFS (HR, 0.44; 95% CI, 0.25–0.80; p = 0.0068) and primary tumor resection (HR, 0.34; 95% CI, 0.18–0.65; p = 0.0010) and serum CA19-9 level (HR, 1.75; 95% CI, 1.02-3.00; p = 0.043) were associated with OS. Conclusions: No significant survival difference was observed between patients administered anti-EGFR mAb re-challenge first and those administered FTD/TPI plus BEV first, whereas the RR of anti-EGFR mAb re-challenge is significantly higher than that of FTD/TPI plus BEV.