FDA approves combination regimen for metastatic colorectal cancer
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The FDA granted an encorafenib-led combination accelerated approval for the treatment of certain patients with metastatic colorectal cancer.
The indication applies to use of the agent for patients with BRAF V600E-mutant metastatic colorectal cancer detected by an FDA-approved test.
Encorafenib (Braftovi, Pfizer) is a BRAF inhibitor.
The FDA based approval on data from the 1:1:1 randomized BREAKWATER trial, which included patients diagnosed with treatment-naive BRAF V600E mutation-positive metastatic colorectal cancer.
The first arm received encorafenib once orally daily with intravenous cetuximab (Erbitux, Eli Lilly & Co.) every 2 weeks, whereas the second arm received the same as arm 1 in addition to a modified FOLFOX6 (mFOLFOX6) chemotherapy regimen every 2 weeks.
The third arm received mFOLFOX6 and FOLFOXIRI (5-FU, folinic acid, oxaliplatin and irinotecan) every 2 weeks, in addition to CAPOX every 3 weeks, with or without bevacizumab (Avastin, Genentech), as a control arm.
Patients received treatment until disease progression, unacceptable toxicity, consent withdrawal, loss to follow-up or death.
Objective response rate (ORR) served as the major efficacy outcome measure, assessed by blinded independent central review in the first 110 patients randomly assigned in each respective arm.
Patients that received the encorafenib plus cetuximab plus mFOLFOX6 arm had a higher ORR than those in the control arm (61% vs 40%).
Patients that received the combination regimen also had a longer median duration of response (13.9 months vs 11.1 months).
Adverse reactions that occurred in at least 25% of patients included peripheral neuropathy, nausea, fatigue, rash, diarrhea, decreased appetite, vomiting, hemorrhage, abdominal pain, and pyrexia.
Grade 3 or 4 lab abnormalities that occurred in at least 20% included increased lipase and decreased neutrophil count.
Researchers determined the recommended dose for encorafenib as 300 mg (four 75 mg capsules) orally once a day in combination with cetuximab and mFOLFOX6 until disease progression of unacceptable toxicity.
Evaluation of PFS and OS are still ongoing.