Safety and Efficacy of Triple Therapy Containing Encorafenib, Cetuximab, and Binimetinib for BRAF V600E-Mutated Colorectal Cancer: a Systematic Review and Meta-Analysis.

[BACKGROUND] BRAF V600E-mutated colorectal cancer (CRC) is associated with poor prognosis and resistance to standard chemotherapy. Emerging evidence, including the BEACON trial and subsequent real-world studies, suggests that triple therapy targeting BRAF oncoprotein, epidermal growth factor receptor (EGFR), and MEK improves clinical outcomes.

[OBJECTIVE] To evaluate the survival, treatment response, and safety outcomes associated with triple therapy comprising encorafenib, cetuximab, and binimetinib in patients with BRAF V600E-mutated CRC.

[METHODS] A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. A comprehensive search of PubMed, Cochrane Central, and ClinicalTrials.gov was performed until October 2024. Proportional outcomes were pooled using inverse-variance logit-transformed random-effects models, and time-to-event outcomes were synthesized using a random-effects survival meta-analysis. Hetrogenity was quantified using I ² statistics. Primary outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), while secondary outcomes focused on safety and adverse events.

[RESULTS] Six studies (one randomized trial, one phase II trial, and four cohort studies) involving 487 patients were included. The pooled 12-month OS rate was 44% (95% CI: 29-66%), with a median OS of 9.75 months (95% CI: 7.22-15.69). The 12-month PFS rate was 13% (95% CI, 7-24%), and the median PFS was 4.89 months (95% CI: 4.22-6.46). The ORR was 35% (95% CI: 27-44%), including a 5% complete response rate and a 32% partial response rate. Grade ≥ 3 adverse events occurred in 46% of the patients, most commonly acneiform dermatitis and diarrhea.

[CONCLUSION] Triple therapy with encorafenib, cetuximab, and binimetinib offers meaningful improvements in survival and tumor response in BRAF V600E-mutated CRC, although the toxicity remains substantial. Optimizing patient selection and managing adverse events are critical for broader clinical use.