BRAFV600E Mutation in First-line Metastatic Colorectal Cancer: an Analysis of Individual Patient Data from the ARCAD Database
A partir des données de 6 391 patients atteints d'un cancer colorectal de stade métastatique inclus dans 10 essais randomisés, cette étude analyse l'effet de la mutation V600E du gène BRAF sur l'efficacité, du point de vue de la survie sans progression et de la survie globale, de l'ajout de thérapies ciblées à une chimiothérapie de première ligne
Background : First-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed at assessing the prognostic and predictive impact of BRAFmt for the efficacy of targeted therapies with first-line chemotherapy. Methods : Individual patient data from first-line RCTs with BRAF and KRAS status data in the ARCAD database were pooled. Progression-free survival and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Outcomes were compared between treatment groups that were concurrently randomized whenever possible. Results : 6391 patients from 10 RCTs were included: 573 BRAFmt (9.0%), 2059 KRASmt (32.2%) and 3759 double wild-type (58.8%). BRAFmt mCRC patients experienced statistically significantly poorer OS than those with KRASmt (adjusted hazard ratio [HRadj] =1.46, 95% confidence interval [95%CI] = 1.30-1.64) and patients with double wild-type tumors (HRadj =2.14, 95%CI = 1.94-2.36). Anti-EGFR agents did not improve progression-free survival or OS of BRAFmt mCRC patients, based on 4 RCTs testing chemotherapy ± anti-EGFR (HRadj =0.96, 95%CI = 0.71-1.30 and HRadj =0.85, 95%CI = 0.66-1.14, respectively). Conclusion : Our data suggest that the addition of anti-EGFR agents to chemotherapy is ineffective as first-line treatment for BRAFmt mCRC patients.