ASCO 25: Braftovi shows "unprecedented" survival gain

A combination regimen based on Pfizer's BRAF inhibitor Braftovi achieved a 51% reduction in the risk of death in patients when used first-line to treat patients with a form of colorectal cancer (CRC), putting it odds-on for a full FDA approval.

Pfizer said in February that the results of the BREAKWATER trial showed that Braftovi (encorafenib) with Eli Lilly's Erbitux (cetuximab) and chemotherapy achieved a significant improvement in both overall survival (OS) and progress-free survival (PFS) compared to chemotherapy given with or without bevacizumab in patients with metastatic, BRAF-V600E-mutated CRC.

At the ASCO congress in Chicago, oncologists got a look at the data behind the earlier headlines, and – according to gastrointestinal cancers expert Joel Saltzman of the Cleveland Clinic – the results have established a new frontline standard of care for this patient population.

"This trial continues to move the needle forward to a more personalised approach to care based on the molecular and genetic characteristics of metastatic colon cancer," he said.

The newly unveiled data show that OS was 30.3 months in the Braftovi arm, 19.5 months for a short-lived second arm looking at Braftovi plus Erbitux, which was cut after a change in protocol, and 15.1 months for the standard-of-care control group. PFS came in at 12.8 months, 6.8 months, and 7.1 months, respectively, representing a 47% reduced risk with the BRAF inhibitor. The data was simultaneously published in the New England Journal of Medicine.

Lead study author Elena Elez, of Vall d'Hebron Institute of Oncology in Barcelona, Spain, said the results were "the first promising survival outcomes ever reported for BRAF-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients."

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.

Combined sales of the drug and companion therapy Mektovi were $607 million from those indications last year. However, accelerated approval for the first-line CRC indication in January of this year – especially if confirmed as a full approval – is expected to put it on a trajectory to reach $1 billion-plus in sales.

BRAF mutations are estimated to occur in just 8% to 10% of people with metastatic colorectal cancer, but tumours carrying them tend to be highly aggressive. V600E is the most commonly encountered BRAF mutation.