New Reference: Encorafenib-Cetuximab with FOLFIRI in bRAF V600E Metastatic Colorectal Cancer

In this phase III randomized study, encorafenib plus cetuximab combined with FOLFIRI significantly improved objective response rate, progression-free survival, and overall survival compared to FOLFIRI with or without bevacizumab in patients with previously untreated BRAF V600E-mutant metastatic colorectal cancer. The safety profile was consistent with known effects of the agents and manageable, supporting encorafenib plus cetuximab with FOLFIRI as a new standard of care option in this population.

Study

Randomised, open-label, global, phase III study [BREAKWATER Cohort 3]

Previously untreated bRAF V600E-mutant metastatic colorectal cancer (mCRC)

Encorafenib + cetuximab (EC) + FOLFIRI (n=73) vs FOLFIRI with or without bevacizumab (control) (n=74)

Efficacy

ORR: 65.8% vs 40.5%(EC + FOLFIRI vs. FOLFIRI) (OR 2.756 [1.420-5.348])

mPFS: 15.2 mos vs 8.3 mos (HR 0.44 [0.27-0.70])

mOS: NE vs 20.3 mos (HR 0.56 [0.34-0.94])

Safety

Grade >=3 AE: diarrhea (12.7% vs 8.8%), anemia (14.1% vs 1.5%), neutropenia (12.7% vs 11.8%), vomiting (2.8% vs 0%), fatigue (2.8% vs 2.9%), constipation (1.4% vs 1.5%), decreased appetite (5.6% vs 2.9%), lipase increased (11.3% vs 5.9%)

Serious AE: 49.3% vs 44.1%

Discontinuation due to AE: 15.5% vs 10.3%