Pfizer’s BRAFTOVI Regimen Approved for Metastatic CRC

Pfizer announced that the FDA has approved BRAFTOVI (encorafenib) in combination with cetuximab (ERBITUX) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) for the treatment of metastatic colorectal cancer (mCRC) patients with a BRAF V600E mutation. This approval, based on the Phase 3 BREAKWATER trial, offers a new treatment option for previously untreated patients with this specific mutation, a subgroup historically with limited treatment choices and poor outcomes.

The approval of this combination therapy follows a significant improvement in response rates and durability of response, showing clinically meaningful results in the BREAKWATER trial, as reported by Pfizer. This study demonstrated a 61% overall response rate (ORR) for patients treated with BRAFTOVI plus cetuximab and mFOLFOX6, compared to 40% for chemotherapy-based treatments. 

“The encorafenib regimen has demonstrated high response rates that are rapid and durable, offering renewed hope for patients with BRAF V600E -mutant mCRC,” said Scott Kopetz, Co-principal Investigator, BREAKWATER trial. 

BRAF V600E mutations, which occur in between 8% and 10% of mCRC cases, significantly worsen prognosis. For these patients, the risk of mortality is more than double that of patients without such mutations. Prior to this approval, no biomarker-driven therapies had been approved for first-line treatment of BRAF V600E -mutant mCRC, highlighting the importance of this new development in the cancer treatment landscape.

Pfizer’s accelerated approval also benefits from FDA’s Project FrontRunner, which aims to expedite the approval of new cancer therapies for advanced or metastatic diseases. The approval utilized the Real-Time Oncology Review (RTOR) pilot program and Project Orbis, with regulatory reviews continuing in other countries, including Canada and Brazil.

“The approval of this first-line treatment option represents a milestone in our mission to deliver targeted therapies for cancers driven by genetic mutations,” said Chris Boshoff, Chief Oncology Officer, Pfizer. “This development further strengthens our commitment to patients with BRAF-driven cancers, which have historically been among the most difficult to treat,” he added. 

As the third most common type of cancer worldwide, colorectal cancer (CRC) is diagnosed in nearly 1.8 million people annually. Approximately 20% of CRC patients will have metastatic disease, which makes it harder to treat. 

In Mexico, 15,000 new cases of colon and/or rectum cancer (CRC) are diagnosed annually, according to IMSS. This type of cancer is the second most common cancer suffered by Mexican men and the fourth most common among women. The Centro Médico Nacional (CMN) Oncology Hospital reports it receives 10% more cases each year of CRC.