Pfizer Reports Positive Progression Free Survival Data From BREAKWATER Trial OBRAFTOVI® In BRAF V600E Metastatic Colorectal Cancer

Pfizer Inc. has reported positive topline progression-free survival (PFS) results from Cohort 3 of the pivotal BREAKWATER study. The cohort evaluated BRAFTOVI in combination with Erbitux and FOLFIRI (fluorouracil, leucovorin, and irinotecan) in patients with previously untreated metastatic colorectal cancer (mCRC) harbouring a BRAF V600E mutation.

The combination regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with FOLFIRI alone or with bevacizumab, as assessed by blinded independent central review (BICR). Overall survival (OS), evaluated as a descriptive secondary endpoint, also showed clinically meaningful improvement in favour of the BRAFTOVI-based regimen.

“These results build on the positive objective response rate data we recently shared, providing further evidence of the meaningful benefit this BRAFTOVI-based targeted approach may offer patients with BRAF V600E–mutant metastatic colorectal cancer,” said Jeff Legos, Chief Oncology Officer, Pfizer. “The combination of significant responses and now improvement in progression‑free survival underscores the potential of BRAFTOVI as a potentially practice-changing treatment option for patients and families facing this challenging diagnosis.”

The primary endpoint for this cohort was objective response rate (ORR) per BICR, which was met. These ORR findings were recently presented at the ASCO GI Cancers Symposium. At the time of the PFS analysis, the safety profile of the triplet combination was consistent with those of its components, with no new safety signals identified.

The combination of BRAFTOVI, cetuximab, and FOLFIRI remains investigational and is not yet approved. Detailed data from this cohort will be submitted for presentation at an upcoming medical meeting and shared with the U.S. Food and Drug Administration to support a potential regulatory submission.

Notably, BRAFTOVI in combination with cetuximab and mFOLFOX6 received accelerated approval from the FDA in December 2024 for treatment-naïve patients with BRAF V600E-mutant mCRC. Continued approval is contingent upon confirmation of clinical benefit in ongoing analyses.