Meta-analysis of triplet therapy in BRAFV600E-mutated mCRC

Presented by

Dr Davi Said G. Celso, Federal University of Viçosa, Brazil

Conference

ESMO GI 2024

Doi
https://doi.org/10.55788/750747ee

A systematic review and meta-analysis examined the safety and efficacy data from 8 trials using encorafenib, binimetinib, and cetuximab triplet therapies as first-line treatment options for patients with metastatic colorectal cancer (mCRC), and observed high heterogeneity in the results.

The BRAF^V600E mutation in mCRC, present in 5–21% of patients depending on the study population, is associated with a poor prognosis. On the other hand, this mutation can also predict a positive response to targeted therapy. Recent evaluations of a triplet therapy strategy including encorafenib, binimetinib, and cetuximab, have shown promising efficacy results, particularly in the BEACON CRC trial (NCT02928224) [1].

After conducting a systematic review, Dr Davi Said G. Celso (Federal University of Viçosa, Brazil) and colleagues performed a single-arm meta-analysis to pool the proportions of binary outcomes and their respective 95% confidence intervals [2]. The analysis included 8 studies with a total of 489 participants. Among these participants, 45.7% were men, 52.4% had an ECOG status of 0, 10.1% had high microsatellite instability, 72.1% received at least 1 line of previous therapy, and 61.5% presented with liver metastases.

The pooled proportions for 12-month and 24-month overall survival were 0.35 (95% CI 0.14–0.64) and 0.07 (95% CI 0.01–0.27), respectively. The 12-month progression-free survival rate was 0.08 (95% CI 0.03–0.20). The pooled overall response rate was 0.34 (95% CI 0.25–0.42). Adverse events leading to drug discontinuation and death occurred in 16% (95% CI 0.09–0.27) and 3% (95% CI 0.02–0.06) of the participants, respectively, while serious adverse events were reported in 53% (95% CI 0.48–0.59) of cases. The most common adverse events included diarrhoea (62.1%), dermatitis acneiform (49.6%), and nausea (47.3%).

The results of this analysis suggest that triplet therapy with encorafenib, binimetinib, and cetuximab can be a safe and effective strategy for patients with BRAF^V600E-mutated mCRC, across a diverse population from 8 trials. However, the high heterogeneity observed indicates a lack of uniformity in study designs across those trials, highlighting the need for further research to standardise treatment protocols.

Kopetz S, et al. N Engl J Med 2019;381(17):1632-1643.
Celso DSG, et al. Safety and Efficacy of Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer: A Systematic Review and Single-Arm Meta-Analysis. Abstract 61P, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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