BRAF V600EMutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data from the ARCAD Database

Romain Cohen, Heshan Liu, Jack Fiskum, Richard Adams, Benoist Chibaudel, Timothy S. Maughan, Eric Van Cutsem, Alan Venook, Jean Yves Douillard, Volker Heinemann, Cornelis Ja Punt, Alfredo Falcone, Carsten Bokemeyer, Richard Kaplan, Heinz Josef Lenz, Miriam Koopman, Takayuki Yoshino, John Zalcberg, Alex Grothey, Aimery De GramontQian Shi, Thierry André

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1386-1395
Number of pages10
JournalJournal of the National Cancer Institute
Issue number10
StatePublished - Oct 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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