Originally published by our sister publication Clinical Oncology News
The FDA granted accelerated approval to encorafenib (Braftovi, Array BioPharma, a subsidiary of Pfizer) with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.
Efficacy was evaluated in BREAKWATER (ClinicalTrials.gov. Identifier: NCT04607421), an active-controlled, open-label, multicenter trial. Patients were required to have treatment-naive BRAF V600E mutation−positive mCRC, detected by the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction kit. Patients were initially randomized 1:1:1 to one of the following treatment arms:
• encorafenib orally once daily with cetuximab IV infusion every two weeks (encorafenib + cetuximab arm);
• encorafenib orally once daily with cetuximab IV infusion every two weeks and mFOLFOX6 (modified folinic acid, fluorouracil and oxaliplatin) every two weeks (encorafenib + cetuximab + mFOLFOX6 arm) or
• mFOLFOX6, FOLFOXIRI (FOLFOX and irinotecan) (both every two weeks) or CAPOX (capecitabine and oxaliplatin) (every three weeks)-each with or without bevacizumab (control arm).
The trial was subsequently amended to limit randomization (1:1) to the encorafenib + cetuximab + mFOLFOX6 arm and the control arm. Treatment in all arms continued until disease progression, unacceptable toxicity, consent withdrawal, lost to follow-up or death. The results of the encorafenib + cetuximab + mFOLFOX6 arm compared with the control arm served as the basis of the accelerated approval and are described below.
The major efficacy outcome measure was confirmed objective response rate (ORR) assessed by blinded independent central review and evaluated in the first 110 patients randomized in each arm. The ORR was 61% (95% CI, 52%-70%) in the encorafenib + cetuximab + mFOLFOX6 arm and 40% (95% CI, 31%-49%) in the control arm. The median duration of response was 13.9 months (95% CI, 8.5 months to not estimable) and 11.1 months (95% CI, 6.7-12.7 months) in the respective arms.
The most common adverse reactions (≥25%) were peripheral neuropathy, nausea, fatigue, rash, diarrhea, decreased appetite, vomiting, hemorrhage, abdominal pain and pyrexia. The most common grade 3 or 4 laboratory abnormalities (≥20%) were increased lipase and decreased neutrophil count.
The full prescribing information for Braftovi is posted here.
—Clinical Oncology News Staff
Based on a press release from the FDA.
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