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.