BRAFV600E Mutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data From the ARCAD Database. (18th March 2021)

• Record Type: Journal Article
• Authors: Cohen, Romain; Liu, Heshan; Fiskum, Jack; Adams, Richard; Chibaudel, Benoist; Maughan, Timothy S; Van Cutsem, Eric; Venook, Alan; Douillard, Jean-Yves; Heinemann, Volker; Ja Punt, Cornelis; Falcone, Alfredo; Bokemeyer, Carsten; Kaplan, Richard; Lenz, Heinz-Josef; Koopman, Miriam; Yoshino, Takayuki; Zalcberg, John; Grothey, Alex; de Gramont, Aimery; Shi, Qian; André, Thierry
• Is Part Of: Journal of the National Cancer Institute. Volume 113:Number 10(2021)
• Page Start: 1386
• Page End: 1395
• Publication Date: 2021-03-18
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djab042
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: First-line therapeutic strategies for patients with BRAF V600E -mutated ( BRAF mt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed to assess the prognostic and predictive impact of BRAF mt 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 BRAF mt (9.0%), 2059 KRAS mt (32.2%), and 3759 double wild type (58.8%). BRAF mt mCRC patients experienced statistically significantly poorer OS than those with KRAS mt (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 BRAF mt 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 BRAF mt mCRC patients.