FDA Grants Accelerated Approval for Encorafenib for BRAF V600E Mutant Metastatic Colorectal Cancer

The US Food and Drug Administration (FDA) has granted accelerated approval to encorafenib with cetuximab and modified FOLFOX6 (fluorouracil, leucovorin, and oxaliplatin; mFOLFOX6) for patients with metastatic colorectal cancer and a BRAF V600E mutation, as detected by an FDA-approved test. This regulatory decision was based on results from the BREAKWATER trial.

The phase 3, active-controlled, open-label BREAKWATER trial enrolled treatment-naïve patients with BRAF V600E mutated metastatic colorectal cancer. The test used to detect mutations was the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction kit. Initially, patients were randomized on a 1-to-1-to-1 basis to receive encorafenib once daily plus cetuximab every 2 weeks; encorafenib plus cetuximab and mFOLFOX6 every 2 weeks; or mFOLFOX6, FOLFIRI every 2 weeks, or CAPOX every 3 weeks, with or without bevacizumab (control arm). The trial was eventually altered to limit randomization to the encorafenib plus cetuximab plus mFOLFOX6 arm and the control arm. The outcome considered in this accelerated approval was the encorafenib plus cetiuximab and mFOLFOX6 arm compared with the control arm.

The confirmed objective response rate (ORR) was assessed by blinded independent central review and included the first 110 patients randomized to each arm. The ORR of the encorafenib plus cetuximab and mFOLFOX6 arm was 61% vs 40% in the control arm. The median duration of response was 13.9 months and 11.1 months respectively. Evaluation of data for progression-free survival and overall survival are still ongoing.

The most common adverse events occurring in ≥ 25% of patients included peripheral neuropathy, nausea, fatigue, rash, diarrhea, decreased appetite, vomiting, hemorrhage, abdominal pain, and pyrexia. The most common grade 3/4 laboratory abnormalities occurring in ≥ 20% of patients were increased lipase and decreased neutrophil count.

The recommended dose of encorafenib is 300 mg orally one every day, in combination with cetuximab and mFOLFOX6 until disease progression or unacceptable toxicity.

Source:

FDA grants accelerated approval to encorafenib with cetuximab and mFOLFOX6 for metastatic colorectal cancer with a BRAF V600E mutation. Accessed on December 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-encorafenib-cetuximab-and-mfolfox6-metastatic-colorectal-cancer-braf