Pfizer reports positive phase 3 results for Braftovi in colorectal cancer

Pfizer has revealed promising results from its phase 3 BREAKWATER trial, showcasing the efficacy of its Braftovi (encorafenib) regimen in treating patients with previously untreated BRAF V600E-mutant metastatic colorectal cancer (CRC). This study involves a combined treatment approach using Braftovi along with Eli Lilly/Merck KGaA’s Erbitux (cetuximab) and the chemotherapy regimen mFOLFOX6, which includes fluorouracil, leucovorin, and oxaliplatin.

The findings from the trial demonstrate that the Braftovi regimen yields significant improvements in both progression-free survival, which is one of the dual primary endpoints, and overall survival, a key secondary endpoint. These results are noteworthy when compared to traditional chemotherapy treatments, with or without the addition of bevacizumab.

In the United States, colorectal cancer is expected to impact approximately 154,270 individuals this year alone. Among these cases, BRAF mutations are present in up to 12% of metastatic CRC cases, presenting a challenging prognosis for these patients. The mutation BRAF V600E, in particular, is linked to a doubling in the risk of mortality compared to patients without this genetic alteration.

Braftovi, an oral kinase inhibitor, specifically targets the BRAF V600E mutation. This drug received accelerated approval from the US Food and Drug Administration (FDA) in December. The approval was based on a significant and clinically relevant improvement in the confirmed objective response rate, another dual primary endpoint of the BREAKWATER study, when used in combination with Erbitux and mFOLFOX6 for patients with previously untreated BRAF V600E-mutant metastatic CRC.

Pfizer plans to present these new findings to the FDA to support a shift from accelerated to full approval of this treatment regimen. The company is also engaging with regulatory bodies worldwide to discuss the data further. Roger Dansey, Pfizer’s chief oncology officer, expressed optimism regarding the impact of these results. He highlighted the potential for these findings to change current treatment practices for a patient population that has faced limited therapeutic options and generally poor outcomes.

Dansey emphasized that the Braftovi regimen is poised to become a standard of care as the first targeted therapy approved for first-line use in patients with metastatic CRC harboring a BRAF V600E mutation. He also conveyed Pfizer’s enthusiasm about working with international health authorities to make this treatment available to more patients globally as soon as possible.

Pfizer holds exclusive rights to market Braftovi in the United States, Canada, Latin America, the Middle East, and Africa. Other companies, such as Ono Pharmaceutical, Medison, and Pierre Fabre, also hold licenses for the drug. As Pfizer proceeds with discussions with global regulatory authorities, the potential for this regimen to transform CRC treatment landscapes becomes increasingly apparent, offering hope to many patients worldwide.