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Adding a BRAF inhibitor and an EGFR antibody to first-line chemotherapy roughly doubled survival in BRAF V600E-mutated metastatic bowel cancer, one of the worst-prognosis subtypes.
Open-label phase 3 trial of patients with untreated BRAF V600E-mutated metastatic colorectal cancer randomised to encorafenib plus cetuximab plus mFOLFOX6, encorafenib plus cetuximab alone (arm later closed), or standard chemotherapy with or without bevacizumab. Primary endpoints were PFS and objective response rate.
The first report (Nature Medicine 2025) showed a response rate of about 61% vs 40%, supporting accelerated FDA approval in December 2024. The 2025 NEJM report showed median PFS 12.8 vs 7.1 months (HR 0.53) and median OS 30.3 vs 15.1 months (HR 0.49). It moved BRAF-targeted therapy from second line (BEACON) to first line and is the largest survival gain ever seen in this subgroup.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
Shares Scott Kopetz, Josep Tabernero, Takayuki Yoshino, BRAF V600E (and V600K).
Shares Elena Élez, Scott Kopetz, Josep Tabernero, Encorafenib.
Shares Elena Élez, Scott Kopetz, Josep Tabernero, Encorafenib.
Shares Scott Kopetz, BRAF V600E (and V600K), Encorafenib, MD Anderson Cancer Center.
Shares Tae Won Kim, Elena Élez, Takayuki Yoshino, Lines of therapy.
Shares Tae Won Kim, Objective response rate (ORR), Progression-free survival (PFS), Acquired resistance to every therapy.
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, BRAF, EGFR.
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Pfizer (incl. Seagen), Monoclonal antibodies.