The Food and Drug Administration (FDA) approved Braftovi (encorafenib) plus Erbitux (cetuximab) and mFOLFOX6 to treat patients with metastatic colorectal cancer with a BRAF V600E mutation.
mFOLFOX6 is a chemotherapy regimen consisting of oxaliplatin plus leucovorin plus fluorouracil, according to the FDA.
The accelerated approval, which was announced by an alert from the FDA, was based on findings from the BREAKWATER trial. The trial included patients with treatment naïve BRAF V600E mutation-positive metastatic colorectal cancer detected by an FDA-approved test, particularly the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction kit.
Initially, patients were randomly assigned to receive either Braftovi with Erbitux every two weeks; Braftovi with Erbitux and mFOLFOX6 every two weeks; or mFOLFOX6, FOLFOXIRI (both every two weeks) or CAPOX (every three weeks). The last arm’s treatment was administered either with or without Avastin (bevacizumab). Eventually the trial was updated to only include the first two treatment assignments.
Patients were treated until unacceptable toxicity, disease progression, lost to follow-up, consent withdrawal or death, according to the alert. The approval was mainly based on results in patients assigned Braftovi with Erbitux and mFOLFOX6 compared with those treated with mFOLFOX6, FOLFOXIRI or CAPOX, which defined the control arm.
The main area of interest was objective response rate. In the trial, the objective response rate was 61% in patients treated with Braftovi with Erbitux and mFOLFOX6 compared with 40% in those in the control arm. The median duration of response was 13.9 months in the treatment arm and 11.1 months in the control arm.
Researchers will also be assessing overall survival and progression-free survival in the ongoing BREAKWATER trial as part of the post-marketing confirmatory evidence for this accelerated approval, according to the alert.
The most common side effects, which occurred in at least 25% of patients, included nausea, peripheral neuropathy, rash, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, bleeding and fever. In addition, the most common grade 3 (severe) or 4 (life-threatening) laboratory abnormalities, occurring in at least 20% of patients, were decreased neutrophil counts and increased lipase counts.
The FDA noted that the recommended dose of Braftovi is 300 milligrams, administered orally (via four 75-milligram capsules) once per day plus Erbitux and mFOLFOX6 until disease progression or unacceptable toxicity.
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