Efficacy of different maintenance strategies for RAS wild-type colorectal cancer: A network meta-analysis

Introduction: In metastatic RAS wild-type colorectal cancer (CRC), induction combination chemotherapy doublets (CT) with an anti-EGFR agent are considered the primary treatment. We performed a network meta-analysis (NMA) to compare the relative efficacy of different maintenance treatments for advanced RAS wild-type CRC. Materials and Methods: PubMed, EMBASE and Cochrane, from database inception until December 2021 were used. Randomized clinical trials enrolling adults with advanced RAS wild-type CRC and providing overall survival (OS) and/or progression-free survival (PFS) data PRISMA guidelines for NMA were followed. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Results: A total of 7 randomized phase 2 trials were included (for a total of 1286 patients). Compared to depotentiation treatments, continuous CT + anti-EGFR was not significantly superior to other maintenance regimens for OS and was ranked as the best option for NMA (SUCRA p-score=0.69). Conversely, in the PFS analysis, single-agent fluoropyrimidines + anti-EGFR was ranked as the best treatment (SUCRA p-score=0.60). Conclusions: Maintaining chemotherapy doublet + anti-EGFR until progression appears to be the best first-line strategy in terms of OS for advanced unresectable RAS wild-type mCRC treatment. However, fluoropyrimidines single-agent + cetuximab or panitumumab represent a reasonable choice regarding PFS.