Effectiveness and safety of encorafenib-cetuximab in BRAFV600E metastatic colorectal cancer: Confidence study.

Abstract

126 Background: BRAFV600E mutant metastatic colorectal cancer (mCRC) has a poor prognosis. The BEACON trial demonstrated an improvement in tumor response, overall survival (OS), and progression-free survival (PFS) when administering encorafenib-cetuximab (EC) to patients (pts) who progressed after 1 or 2 therapy lines. This study provides a retrospective analysis of the effectiveness and safety of EC in the real-world setting in Spain. Methods: This retrospective analysis included BRAFV600E mCRC pts treated with EC in 2nd line treatment, recruited from March to July 2022. The Co-primary study endpoints included effectiveness based on PFS and OS. Secondary endpoints included sociodemographic and clinical characteristics of patients before EC initiation, overall response rate (ORR), and safety. Results: From March to July 2022, 81 evaluable pts were included. Sociodemographic and clinical characteristics are displayed.A median (interquartile range [IQR]) of 6.0 (4.0-13.0) cycles of encorafenib and 6.0 (4.0-14.5) cycles of cetuximab were administered. Median treatment duration was 4.4 (2.6-7.8) months (m) and 4.4 m (2.8-7.6) respectively. The ORR and disease control rate was 33.8 % (CI 95% 23.4-45.5) and 68.8 (CI 95% 57.3 – 78.9) respectively. One (1.2%) pt achieved complete response At data cut-offwith a 9.7 median follow-up, 50 (61.7%) pts had died, all of them due to disease progression. Median (95% Confidence Interval, CI) OS was 12.6 m (8.0-17.3) and median PFS was 5.0 m (3.8-6.2). The 12-m OS and 12-m PFS rates were 54.6% (95% CI, 43.3-65.9) and 19.9% (10.5-29.3) respectively. Pts with neutrophils/lymphocyte ratio (NLR) ≥3 had worse OS (HR, 1.8 95% CI 1.0-3.2; p < 0.049) and worse PFS (HR, 2.3, 1.4-3.8; p < 0.002). Disease progression (86.7%) was the most frequent cause of treatment discontinuation, followed by unacceptable AEs (3.7%). Eleven pts (13.5%) experienced treatment-related graded 3 or 4 AEs, mainly acne (3.7%). Treatment-related deaths were not reported. Conclusions: This study provides real-world data of BRAFV600E mCRC pts treated with EC combination in routine clinical practice in Spain. EC effectiveness and safety were consistent with the results obtained in clinical trials. [Table: see text]