Jnci-Journal Of The National Cancer Institute
Author:
Keywords:
Science & Technology, Life Sciences & Biomedicine, Oncology, KRAS WILD-TYPE, FOLFIRI PLUS BEVACIZUMAB, BRAF MUTATION, POOLED ANALYSIS, RANDOMIZED PHASE-3, RAS MUTATIONS, CETUXIMAB, CHEMOTHERAPY, SURVIVAL, BENEFIT, Colonic Neoplasms, Colorectal Neoplasms, Humans, Mutation, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), Randomized Controlled Trials as Topic, Rectal Neoplasms, Treatment Outcome, BRAF, Colorectal cancer, anti-EGFR, antiangiogenic, prognosis, survival, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis
Abstract:
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 to assess the prognostic and predictive impact of BRAFmt on 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 randomly assigned whenever possible. RESULTS: A total of 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 [CI] = 1.30 to 1.64) and patients with double wild-type tumors (HRadj = 2.14, 95% CI = 1.94 to 2.36). Anti-EGFR agents did not improve progression-free survival or OS of BRAFmt mCRC patients, based on 4 RCTs testing chemotherapy with or without anti-epidermal growth factor receptor (anti-EGFR) (HRadj = 0.96, 95% CI = 0.71 to 1.30; and HRadj = 0.85, 95% CI = 0.66 to 1.14, respectively). CONCLUSIONS: Our data suggest that the addition of anti-EGFR agents to chemotherapy is ineffective as first-line treatment for BRAFmt mCRC patients.