Encorafenib plus cetuximab with or without binimetinib for BRAF V600E metastatic colorectal cancer: Updated survival results from a randomized, three-arm, phase III study versus choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC).

Abstract

4001 Background: BEACON CRC is a randomized, phase 3 study which evaluated the triplet of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) and the doublet of ENCO + CETUX vs. investigator’s choice of irinotecan + CETUX or FOLFIRI + CETUX in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) whose disease had progressed after 1-2 prior regimens in the metastatic setting. Primary endpoints were overall survival (OS) and objective response rate (ORR; by blinded central review) for triplet vs control. In a previous interim analysis, triplet and doublet improved OS and ORR versus standard of care. Here we report on an updated analysis. Methods: Updated analysis includes 6 months of additional follow-up and response data for all randomized pts. The study is ongoing. Results: Pts received triplet (n=224), doublet (n=220), or control (n=221). Median OS was 9.3 months (95% confidence interval [CI]:8.2, 10.8) for triplet and 5.9 months (95% CI:5.1-7.1) for control (hazard ratio [HR] (95% CI): 0.60 (0.47-0.75)). Median OS for doublet was 9.3 months (95% CI: 8.0-11.3) (HR vs. control: 0.61 (0.48-0.77). Confirmed ORR was 26.8% (95% CI: 21.1%-33.1%) for triplet, 19.5% (95% CI: 14.5%-25.4%) for doublet, and 1.8% (95% CI: 0.5%-4.6%) for control. Retrospective subgroup analyses suggested some pts may benefit more from triplet than doublet therapy (Table). Both triplet and doublet showed improved OS compared to control in all subgroups. Adverse events were consistent with prior analysis, with grade ≥3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet and control, respectively. Conclusions: The updated analysis of the BEACON CRC study confirmed that encorafenib + cetuximab with or without binimetinib improved OS and ORR in previously treated pts with BRAF V600E mCRC compared with standard chemotherapy. Clinical trial information: NCT02928224 . [Table: see text]