P-23 Clinical Outcomes of Encorafenib, Binimetinib, and Cetuximab for Pretreated BRAF V600E-mutant Metastatic Colorectal Cancer in the BEACON EAP Follow-Up Study

The triplet combination of encorafenib, cetuximab, plus binimetinib (BEACON triplet regimen) showed survival benefit and a higher response over standard chemotherapy in pretreated patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) in the BEACON CRC study. The BEACON triplet regimen as well as encorafenib plus cetuximab are approved in previously treated patients with BRAF V600E-mutant mCRC in Japan, but with a limited number of Japanese patients treated with the BEACON triplet regimen. An expanded access program (EAP) was prospectively conducted to evaluate efficacy and safety of the BEACON triplet regimen for Japanese patients (JapicCTI-205146). Since it was inadequate to evaluate efficacy parameters including overall survival (OS) due to a median follow-up period in the EAP being only 4.6 months (range: 0.3–10.7), we herein conducted an additional study to evaluate efficacy parameters. The multicenter study retrospectively collected data from the medical record of patients treated with a BEACON triplet regimen who were confirmed alive at the end of the EAP. The study collected patient data from the day after the end of the EAP to December 31, 2021. Key eligibility were patients with BRAF V600E-mutant mCRC who progressed after one or two prior systemic chemotherapy. The primary endpoint was OS, and the secondary endpoints included best overall response (BOR) and progression-free survival (PFS). A total of 81 patients who received the BEACON triplet regimen in the EAP were enrolled from 10 Japanese institutions between Feb and Dec 2020. Of these, 58 patients were alive at the end of the EAP, and 57 patients were included in the follow-up study. The median age was 60 years (range: 20–82). Fifty-four patients (67%) had ECOG PS of 0. The median follow-up was 9.17 months (range: 0.3–22.1). The median duration of treatment with encorafenib, binimetinib, and cetuximab was 4.57 months (range: 0.1–17.8), 3.68 months (range 0.1–16.2), and 4.63 months (range: 0.2–17.7), respectively. The median OS was 10.38 months (95% confidence interval [CI]: 9.00–16.16) and the median PFS was 5.29 months (95%CI: 4.21–5.75). The confirmed ORR was 31.6% (95%CI: 21.4–43.3). Of the 81 patients, 40 patients (49.4%) received subsequent treatment: 2 (2.5%) with surgery, 3 (3.7%) with radiotherapy, and 39 (48.1%) with systemic chemotherapy. As systemic chemotherapy, trifluridine/tipiracil + bevacizumab (16 patients [19.8%]) was used most frequently. The clinical outcomes of the BEACON triplet regimen in the Japanese patients with BRAF V600E-mutant mCRC were consistent with those in the BEACON CRC study. These results support that the BEACON triplet regimen is one of the standard treatment for pretreated Japanese patients with BRAF V600E-mutant mCRC.