FDA Approves Pfizer's BRAFTOVI Regimen for BRAF V600E-Mutant Metastatic Colorectal Cancer

Pfizer Inc. has announced a significant advancement in cancer treatment with the U.S. Food and Drug Administration's approval of BRAFTOVI (encorafenib) used in conjunction with cetuximab and mFOLFOX6 for patients suffering from metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. This approval marks a milestone as it is one of the initial approvals under the FDA's Project FrontRunner, which aims to expedite the development and approval of new cancer therapies for advanced diseases.

The basis for this approval lies in the results of the Phase 3 BREAKWATER trial, which demonstrated a substantial improvement in response rates and response durability for patients who were newly diagnosed with mCRC and treated with the BRAFTOVI combination. The trial showed that the BRAFTOVI regimen achieved a confirmed overall response rate (ORR) of 61%, significantly higher than the 40% ORR seen with standard chemotherapy treatments. Additionally, the median duration of response was longer for the BRAFTOVI combination, lasting 13.9 months compared to 11.1 months with chemotherapy alone.

Scott Kopetz, M.D., Ph.D., FACP, from The University of Texas MD Anderson Cancer Center, highlighted the significance of this development, noting the previously limited treatment options for mCRC patients with BRAF mutations. This new regimen, which can be administered as a first-line treatment, offers a promising new avenue for disease control and optimism for patients.

Chris Boshoff, M.D., Ph.D., from Pfizer, emphasized the company's commitment to innovation in cancer treatment. The approval of the BRAFTOVI regimen reinforces Pfizer's role in developing therapies for some of the most challenging cancers to treat, and the company is exploring further advancements, including a next-generation brain-penetrant BRAF inhibitor.

The safety profile of BRAFTOVI when used with cetuximab and mFOLFOX6 aligns with the known profiles of these individual agents. Common side effects observed in the trial included peripheral neuropathy, nausea, fatigue, and diarrhea, among others. A small percentage of patients discontinued BRAFTOVI due to adverse reactions, such as elevated lipase levels.

Michael Sapienza, CEO of the Colorectal Cancer Alliance, expressed optimism regarding the approval, as it introduces a novel treatment option for patients with a particularly aggressive form of mCRC associated with the BRAF V600E mutation. This development is hailed as a crucial step forward in addressing the unmet needs of this patient community.

The application for BRAFTOVI was granted priority review and utilized the Real-Time Oncology Review pilot program, also forming part of Project Orbis, which includes ongoing reviews in countries like Canada and Brazil. This approval follows an earlier FDA authorization for BRAFTOVI in combination with cetuximab for mCRC patients with BRAF V600E mutations after prior therapy.

Colorectal cancer is a prevalent form of cancer globally, with significant incidence and mortality rates. BRAF mutations occur in a minority of mCRC cases but are associated with poor prognoses. The BRAF V600E mutation, in particular, has been linked to higher mortality rates, and until now, specific biomarker-driven therapies for untreated patients with this mutation were unavailable.

The BREAKWATER trial represents a crucial step in evaluating the effectiveness of BRAFTOVI for previously untreated mCRC patients harboring the BRAF V600E mutation. With promising results from this trial, future medical meetings will present further data, which will help guide the potential global expansion of this treatment option.

Pfizer retains exclusive rights to market BRAFTOVI in several regions, while other pharmaceutical companies hold rights in additional territories, ensuring the broad availability of this innovative treatment. The approval of BRAFTOVI exemplifies Pfizer's dedication to addressing cancer's most challenging forms through groundbreaking therapies.