SO-29 Clinical characteristics, efficacy, and safety in patients receiving second- or third-line encorafenib plus cetuximab (E+C) vs control for metastatic colorectal cancer (mCRC): BEACON CRC post hoc analysis

BRAF mutations occur in 8% to 12% of patients with mCRC and are associated with clinically poor prognosis. E+C was approved by the FDA and EMA for patients with BRAF V600E-mutant mCRC who have received prior systemic therapy based on the results of the BEACON study (NCT02928224), which combined patients treated in the second- (2L) and third-line (3L) setting. Here we evaluate the characteristics and outcomes separately for patients who received 2L and 3L E+C or control. BEACON was a phase 3, open label study evaluating E (300 mg QD) plus C (400 mg/m 2 initial dose followed by 250 mg/m 2 weekly) with or without binimetinib (45 mg BID) vs control (C plus irinotecan or FOLFIRI). The primary study endpoint was OS. For this post hoc analysis (data cutoff: November 10, 2022), patients receiving E+C or control were grouped by line of therapy (2L and 3L). A total of 291 patients received 2L treatment (n=146 E+C; n=145 control); median age was 60 and 59 years, 45.9% and 49.0% had ECOG PS 1, and 45.2% and 44.1% had ≥3 organs involved at baseline. Of those who received 3L treatment (n=74 E+C; n=76), median age was 62 and 61 years, 50.0% and 55.3% had ECOG PS 1, and 50.0% and 44.7% had ≥3 organs involved at baseline. For 2L, the OS HR [95% CI] was 0.60 [0.46, 0.78]; P P P =0.0057 (median OS: 7.9 and 4.8 months for E+C and control); the PFS HR [95% CI] was 0.43 [0.29, 0.66]; P < 0.0001 (median PFS: 4.2 and 1.5 months). In 2L, 31 (21.2%) vs 3 (2.1%) patients for E+C vs control were confirmed responders. For 3L, 14 (18.9%) vs 1 (1.3%) patients for E+C vs control were confirmed responders. Of patients who received 2L treatment, 91 patients (62.3%) in the E+C group, and 77 patients (53.1%) in the control group received subsequent therapy. Of those who received 3L treatment, 35 patients (47.3%) in the E+C group and 34 patients (44.7%) in the control group received subsequent therapy. The most common all-causality AEs (≥30% in the E+C arm) in the 2L (E+C vs control) were diarrhea, nausea, dermatitis acneiform, abdominal pain, and fatigue. In the 3L, these were fatigue, diarrhea, nausea, decreased appetite, and anemia. E+C is an effective treatment regimen for patients with BRAF V600E-mutant mCRC in the 2L and 3L setting. In the BEACON CRC study, patient characteristics and outcomes were generally similar between those who received E+C in 2L and those who received it in 3L. First-line E+C with or without chemotherapy is currently under investigation in the BREAKWATER study (NCT04607421).