Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial

Kopetz, S; Yoshino, T; Van Cutsem, E; Eng, C; Kim, TW; Wasan, HS; Desai, J; Ciardiello, F; Yaeger, R; Maughan, TS; Beyzarov, E; Zhang, X; Ferrier, G; Zhang, X; Tabernero, J

Author(s): Kopetz, S; Yoshino, T; Van Cutsem, E; Eng, C; Kim, TW; Wasan, HS; Desai, J; Ciardiello, F; Yaeger, R; Maughan, TS; Beyzarov, E; Zhang, X; Ferrier, G; Zhang, X; Tabernero, J;
Details: Publication Year 2025-03,Volume 31,Issue #3,Page 901-908
Journal Title: Nature Medicine
Publication Type: Research article
Abstract: Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403-4.253; 99.8% CI: 1.019-5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318-0.691; repeated CI: 0.166-1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421 .
Publisher: Springer Nature
Keywords: Humans; *Colorectal Neoplasms/drug therapy/genetics/pathology; *Proto-Oncogene Proteins B-raf/genetics; *Cetuximab/administration & dosage/therapeutic use/adverse effects; Male; Female; Middle Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Sulfonamides/therapeutic use/administration & dosage/adverse effects; Aged; *Carbamates/therapeutic use/administration & dosage/adverse effects; *Mutation; Adult; *Leucovorin/therapeutic use/administration & dosage/adverse effects; *Fluorouracil/therapeutic use/administration & dosage/adverse effects; Organoplatinum Compounds/therapeutic use/administration & dosage; Aged, 80 and over; Progression-Free Survival
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1038/s41591-024-03443-3
Open Access at Publisher's Site: https://doi.org/10.1038/s41591-024-03443-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-30 02:31:27

Last Modified: 2025-04-08 06:06:11