Pfizer has reported significant findings from its Phase 3 BREAKWATER trial, revealing that the Braftovi (encorafenib) combination regimen reduces the risk of death by 51% in patients with BRAF V600E-mutant metastatic colorectal cancer.
The study evaluated Braftovi in combination with cetuximab and mFOLFOX6, which showed notable survival benefits compared to standard chemotherapy, regardless of bevacizumab.
In the second interim analysis, patients receiving Braftovi regimen showed a median overall survival of 30.3 months, compared to 15.1 months for those on standard chemotherapy.
The combination improved the progression-free survival by reducing the risk of disease progression or death by 47% compared to standard chemotherapy.
Median progression-free survival was 12.8 months with the Braftovi regimen, compared to 7.1 months for chemotherapy alone.
The objective response rate confirmed improvements with the Braftovi combination, maintaining the median duration of response and time to response from previous analyses.
The safety profile of the regimen remained consistent with known profiles of the individual agents, with no new safety signals identified.
Common side effects included nausea, anaemia, diarrhoea, decreased appetite, vomiting, neutrophil count decrease, arthralgia, and rash.
Among patients on the Braftovi regimen, 13.8% experienced adverse reactions leading to permanent discontinuation of Braftovi.
BREAKWATER trial co-principal investigator Elena Élez said: “Patients with metastatic colorectal cancer whose tumours harbour a BRAF V600E mutation generally face a daunting prognosis, as this aggressive tumour often does not respond well to standard-of-care chemotherapy.
“The BREAKWATER results are 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 is an oral small-molecule kinase inhibitor targeting BRAF V600E, which is involved in inappropriate activation of the MAPK signalling pathway in certain cancers, including colorectal cancer.
Pfizer holds exclusive rights to Braftovi in the US, Canada, Latin America, the Middle East, and Africa, while Ono Pharmaceutical, Medison, and Pierre Fabre in other regions.
In December last year, the US Food and Drug Administration (FDA) approved the Braftovi combination to treat BRAF V600E-mutant colorectal cancer under its accelerated pathway.
The approval was based on improvement in objective response rate in treatment-naïve patients, and continued approval is contingent on verification of clinical benefit.
Pfizer chief oncology development officer Johanna Bendell said: “The Braftovi combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with metastatic colorectal cancer with a BRAF V600E mutation.
“These unprecedented results from the BREAKWATER trial further establish the benefit of the Braftovi combination regimen and its potential to become a new standard-of-care, building on Pfizer’s legacy in precision medicine and commitment to delivering breakthrough medicines that help people with cancer live better and longer lives.”
