COLORECTAL CANCER: The combination of encorafenib, binimetinib and cetuximab (triple therapy) improved survival in BRAF V600E mutant disease with manageable toxicity and minimal impact on quality of life

Kevin Sovet

Feb. 3, 2020


COLORECTAL CANCER:  The combination of encorafenib, binimetinib and cetuximab (often referred to as triple therapy) improved survival in BRAF V600E mutant disease with manageable toxicity and minimal impact on quality of life. This combination is under FDA priority review; outcome expected April 2020.

Encorafenib plus cetuximab with or without binimetinib for BRAF V600E–mutant metastatic colorectal cancer: Expanded results from a randomized, 3-arm, phase III study vs the choice of either irinotecan or FOLFIRI plus cetuximab

J Tabernero et al; Annals of Oncology, Volume 30, Issue Supplement_5, October 2019, mdz394.021


Encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) significantly improved overall survival (OS, HR:0.52, P < 0.0001) and objective response rates (ORR, 26% vs 2%, P < 0.0001) in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) compared with current standard of care. This analysis focuses on the triplet ((ENCO+CETUX+BINI) and doublet (ENCO+CETUX) arms.


The BEACON CRC study was a randomized, 3-arm, phase 3 study which evaluated triplet or doublet vs. investigator’s choice of irinotecan or FOLFIRI + CETUX in 665 pts with BRAFV600E mCRC. The triplet vs doublet efficacy comparison was a secondary endpoint (not formally powered). Analyses included efficacy (OS, ORR, depth of response, and progression-free survival [PFS]), multivariate modeling, safety, and quality of life (QOL) assessments (EORTC QOL Questionnaire (QLQ C30), Functional Assessment of Cancer Therapy Colon Cancer, EuroQol 5D 5L, and Patient Global Impression of Change).


224 and 220 pts were randomized to triplet and doublet, respectively. Median overall survival for triplet and doublet was 9.0 (95%CI: 8.0, 11.4) and 8.4 months (95%CI: 7.5, 11.0), respectively (HR:0.79 [95%CI: 0.59, 1.06]). ORR was 26% (95%CI: 18%, 35%) for triplet and 20% (95%CI: 13%,29%) for doublet. For pts with 1 prior therapy, ORR was 34% (95%CI: 23, 47) for triplet and 22% (95%CI: 14, 33) for doublet. Waterfall plots indicated that depth of response favored triplet. Grade 3+ adverse events (AE) were 58% in triplet and 50% in doublet. Rates of discontinuation due to an AE were similar (triplet: 7%; doublet: 8%), with median relative dose intensity maintained for both arms. There were no differences in QOL across 4 instruments. Some toxicities occurred less frequently with the triplet.


In BEACON CRC, triplet and doublet showed encouraging activity in BRAFV600E mCRC. Data suggest that the triplet offers improved efficacy vs doublet with some additional manageable toxicity and no impact on overall QOL. Further follow-up will better define the relative benefits of the regimens.