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BRAF V600E mutation in first-line metastatic colorectal cancer: an analysis of individual patient data from the ARCAD database

Cohen, Romain, Liu, Heshan, Fiskum, Jack, Adams, Richard, Chibaudel, Benoist, Maughan, Timothy S, Van Cutsem, Eric, Venook, Alan, Douillard, Jean-Yves, Heinemann, Volker, Punt, Cornelis J A, Falcone, Alfredo, Bokemeyer, Carsten, Kaplan, Richard, Lenz, Heinz-Josef, Koopman, Miriam, Yoshino, Takayuki, Zalcberg, John, Grothey, Alex, de Gramont, Aimery, Shi, Qian and André, Thierry 2021. BRAF V600E mutation in first-line metastatic colorectal cancer: an analysis of individual patient data from the ARCAD database. JNCI: Journal of the National Cancer Institute 113 (10) , 1386–1395-1395. 10.1093/jnci/djab042

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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 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: Oxford University Press
ISSN: 0027-8874
Date of First Compliant Deposit: 10 May 2021
Date of Acceptance: 12 March 2021
Last Modified: 13 May 2022 13:30
URI: https://orca.cardiff.ac.uk/id/eprint/141023

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