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Clinical Trial
. 2021 Feb 1;39(4):273-284.
doi: 10.1200/JCO.20.02088.

Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study

Josep Tabernero  1 , Axel Grothey  2 , Eric Van Cutsem  3 , Rona Yaeger  4 , Harpreet Wasan  5 , Takayuki Yoshino  6 , Jayesh Desai  7 , Fortunato Ciardiello  8 , Fotios Loupakis  9 , Yong Sang Hong  10 , Neeltje Steeghs  11 , Tormod Kyrre Guren  12 , Hendrik-Tobias Arkenau  13 , Pilar Garcia-Alfonso  14 , Elena Elez  1 , Ashwin Gollerkeri  15 , Kati Maharry  15 , Janna Christy-Bittel  15 , Scott Kopetz  16
Affiliations
Clinical Trial

Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study

Josep Tabernero et al. J Clin Oncol. .

Abstract

Purpose: BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data.

Methods: In this open-label, phase III trial, 665 patients with BRAF V600E-mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients.

Results: Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR v control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively.

Conclusion: In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with BRAF V600E mCRC.

Trial registration: ClinicalTrials.gov NCT02928224.

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Figures

FIG 1.
FIG 1.
Overall survival results. (A) ENCO/BINI/CETUX versus control. (B) ENCO/CETUX versus control. ENCO/BINI/CETUX, encorafenib, binimetinib plus cetuximab; ENCO/CETUX, encorafenib plus cetuximab; HR, hazard ratio; OS, overall survival.
FIG 2.
FIG 2.
Subgroup analysis of overall survival. (A) ENCO/BINI/CETUX versus control. (B) ENCO/CETUX versus control. (C) ENCO/BINI/CETUX versus ENCO/CETUX. CEA, carcinoembryonic antigen; CRP, C-reactive protein; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ENCO/BINI/CETUX, encorafenib, binimetinib plus cetuximab; ENCO/CETUX, encorafenib plus cetuximab; MSI, microsatellite instability.
FIG 3.
FIG 3.
Progression-free survival by blinded independent central review. (A) ENCO/BINI/CETUX versus control. (B) ENCO/CETUX versus control. ENCO/BINI/CETUX, encorafenib, binimetinib plus cetuximab; ENCO/CETUX, encorafenib plus cetuximab; HR, hazard ratio; PFS, progression-free survival.
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