BRAF V600E-Mutant Colorectal Cancers with Liver-Only Metastases: A Retrospective Study.

Abstract BACKGROUND BRAF V600E-mutant colorectal cancers (CRCs) are associated with shorter survival than BRAF wild-type tumors. Therapeutic decision-making for colorectal liver metastases (CRLM) harboring this mutation remains difficult due to the scarce literature. Our aim was to study a large cohort of BRAF V600E-mutant CRLM patients in order to identify prognostic factors associated with overall survival. METHODS We retrospectively identified BRAF V600E-mutant CRCs diagnosed with liver-only metastases, resected or not, between April 2008 and December 2017, in 25 French centers. Clinical, molecular, pathological characteristics and treatment features were collected. Overall survival (OS) was defined as the time from CRLM diagnosis to death from any cause. Cox proportional hazard models were used for statistical analysis. RESULTSAmong the 105 patients included, 79 (75%) received chemotherapy, 18 (17%) underwent upfront CRLM surgery, and 8 (8%) received exclusive best supportive care. CRLM surgery was performed in 49 (46.7%) patients. CRLM were mainly synchronous (90%) with bilobar presentation (61%). The median OS was 34 months (range, 28.9–67.3 months) for resected patients and 10.6 (6.7–12.5) months for unresected patients ( P < 0.0001). Most patients received doublet chemotherapy (72%), and 34% received a combination with bevacizumab as a first-line treatment. In multivariate analysis, primary tumor surgery (hazard ratio (HR) = 0.349; 95% confidence interval (CI) 0.164–0.744, P = 0.0064) and CRLM resection (HR = 0.169; 95% CI 0.082–0.348, P < 0.0001) were associated with significantly better OS. CONCLUSIONSIn the era of systemic cytotoxic chemotherapies, liver surgery seems to extend OS. Therefore, CRLM resectability should be assessed, regardless of mutational status.