61P - Safety and efficacy of encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer: A systematic review and single-arm meta-analysis

Background

BRAF V600E mutation in Colorectal Cancer (CRC) is associated with poor prognosis, and is present in 5 to 21% of patients with metastatic CRC, although it can be a positive predictor of benefit for a targeted therapy. Recent studies evaluated the triplet strategy including encorafenib, binimetinib, and cetuximab, and showed promising results. Therefore, we aim to perform a systematic review and meta-analysis investigating survival and oncological outcomes of the triplet therapy for mCRC patients.

Methods

We searched PubMed, Embase, and Cochrane Central for clinical trials evaluating the use of encorafenib, binimetinib, and cetuximab in patients with BRAF V600E mutated colorectal cancer. The outcomes evaluated were Objective Response Rate (ORR), Adverse Events (AE), Overall Survival (OS) and Progression Free Survival (PFS). We performed a single-arm meta-analysis to pool the proportions of binary outcomes and their respective 95% confidence intervals (CI). Statistical analyses were performed using R software version 4.3.1 with a random-effects model. I² analysis was used to assess heterogeneity. PROSPERO registration: CRD42024499087.

Results

8 studies were included, with a total of 489 patients. 45.7% (179/392) were male, 52.4% (248/473) had an ECOG status of 0, 10.1% (30/297) had high microsatellite instability, 72.1% (341/473) received at least one line of previous therapy, and 61.5% (241/392) presented liver metastasis. Pooled proportions for 12 and 24 month OS were 0.35 (CI 0.14-0.64; I² = 95%) and 0.07 (CI 0.01-0.27; I² = 93%), while 12 month PFS was 0.08 (CI 0.03-0.20; I² = 81%). Pooled ORR was 0.34 (CI 0.25-0.42; I² = 66%). The frequency of AEs leading to drug discontinuation and death were 0.16 (CI 0.09-0.27; I² = 83%) and 0.03 (CI 0.02-0.06; I² = 0%), respectively, while the frequency of serious AEs was 0.53 (CI 0.48-0.59; I² = 0%). Most common AEs were diarrhea (62.1%, 238/383), dermatitis acneiform (49.6%, 190/383), and nausea (47.3%, 181/383).

Conclusions

Our study suggest that triplet therapy can be a safe and effective strategy for patients with BRAF V600 mutated metastatic colorectal cancer, although high heterogeneity suggests a lack of uniformity regarding study designs.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.