Targeted doublet therapy with encorafenib and cetuximab for BRAF V600E-mutant metastatic colorectal cancer: A systematic review and meta-analysis.

BACKGROUND

BRAF V600E-mutated metastatic colorectal cancer (mCRC) represents a biologically aggressive subset with poor prognosis and limited response to conventional therapies. While dual inhibition of BRAF and EGFR with encorafenib and cetuximab has emerged as a promising therapeutic strategy, a comprehensive quantitative synthesis of its efficacy and safety has been lacking.

METHODS

We conducted a systematic review and meta-analysis of studies evaluating the efficacy and safety of encorafenib combined with cetuximab in BRAF V600E-mutated mCRC. Nine studies were included: three randomized trials, one non-randomized early-phase interventional study, and five real-world cohort studies. Data were extracted from randomized controlled trials and cohort studies. A random-effects model was used to pool survival data through reconstructed KM-curves data, treatment response rates, and adverse events. Heterogeneity and publication bias were assessed using I² statistics, Baujat plots, and LFK indices.

RESULTS

This study included 1063 patients from 9 studies. The pooled mean overall survival was 8.7 months (95 % CI: 6.7-12.0), with OS rates at 6, 12, and 18 months of 65 %, 35 %, and 18 %, respectively. Median progression-free survival was 3.7 months (95 % CI: 2.8-4.6). The pooled objective response rate was 25 % (95 % CI: 22-30 %), while partial and complete response rates were 22 % and 2 %, respectively. Disease control was achieved in 67 % of patients (95 % CI: 58-76 %), and 30 % experienced grade ≥ 3 adverse events.

CONCLUSIONS

This meta-analysis supports the use of encorafenib plus cetuximab as an effective and tolerable regimen in patients with BRAF V600E-mutated mCRC, offering modest improvements in survival and disease control. Future trials should prioritize biomarker-guided treatment, explore triplet and first-line combinations, and address mechanisms of resistance to enhance durable clinical benefit.