Pfizer builds on Braftovi bowel cancer OK with survival data

Pfizer only picked up an accelerated approval from the FDA for its Braftovi-based combination regimen for colorectal cancer last month, and it already has survival data that could see that converted to a full license.
The new results from the BREAKWATER study – which is testing the combination of BRAF inhibitor Braftovi (encorafenib) with Eli Lilly's Erbitux (cetuximab) and chemotherapy – showed a significant improvement in progress-free survival (PFS) compared to chemotherapy with or without bevacizumab, as well as an increase in overall survival (OS), when used as a first-line treatment for colorectal cancer with BRAF V600E mutations.
Both results were "clinically meaningful," according to a Pfizer statement, in which chief oncology officer Roger Dansey said that the Braftovi regimen has "the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes."
The combination was cleared by the FDA based on an objective response rate (ORR) of 61% from BREAKWATER, compared to 40% in the control arm, which was presented at the ASCO GI congress last month and simultaneously published in the journal Nature Medicine.
It was one of the first approvals under the FDA's recently launched Project FrontRunner, which is intended to speed up the development and approval of new cancer drugs for advanced or metastatic disease by allowing a review based on a single clinical trial.
The Braftovi regimen also became the first featuring a BRAF-targeted therapy to be approved for first-line treatment of this type of colorectal cancer.
It is a niche indication, given that BRAF mutations are estimated to occur in just 8% to 10% of people with metastatic colorectal cancer, but an important development for patients as these tumours tend to be highly aggressive. V600E is the most commonly encountered BRAF mutation.
Braftovi – which Pfizer acquired through its $11.4 billion takeover of Array Biopharma in 2019 – was previously approved in combination with MEK inhibitor Mekinist (binimetinib) for unresectable or metastatic BRAF-positive melanoma and non-small cell lung cancer (NSCLC), and as a second-line therapy in combination with Erbitux for BRAF-positive colorectal cancer.
It has grown into a mid-range product for Pfizer, with sales of $437 million in the first nine months of 2024, but some analysts believe rising use in NSCLC and the broader colorectal cancer indication could help sales rise towards or possibly even exceed the $1 billion-a-year threshold.
The new OS data could make a difference in encouraging uptake in the latter cancer – assuming doctors are persuaded to carry out BRAF mutation testing more widely.