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The FDA has granted approval of a new indication for cetuximab plus encorafenib for the treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation, as detected by a FDA-approved test, after prior therapy.
The FDA has granted approval of a new indication for cetuximab (Erbitux) plus encorafenib (Braftovi) for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by a FDA-approved test, after prior therapy.1
Cetuximab is the first and only anti-EGFR antibody with regulatory approval, in combination with encorafenib, for this indication, according to Eli Lilly and Company.
The regulatory decision is supported by findings from the phase 3 BEACON CRC trial (NCT02928224), in which the doublet (n = 220) resulted in a median overall survival (OS) of 8.4 months (95% CI, 7.5-11.0) vs 5.4 months (95% CI, 4.8-6.6) with irinotecan plus cetuximab or FOLFIRI with cetuximab (n = 221; HR, 0.60; 95% CI, 0.45-0.79; P = .0003).
The median progression-free survival (PFS) per blinded independent central review (BICR) in the investigative arm was 4.2 months (95% CI, 3.7-5.4) vs 1.5 months (95% CI, 1.4-1.7) in the control arm (HR, 0.40; 95% CI,0.31-0.52; P < .0001).
Moreover, the combination of cetuximab and encorafenib was also found to elicit an objective response rate of 20% (95% CI, 13%-29%) per BICR vs 2% (95% CI, 0%-7%) with the control (P < .0001). Among those who responded to treatment in the investigative arm, 5% experienced a complete response and 15% achieved a partial response. The median duration of response was 6.1 months (95% CI, 4.1-8.3)
"The BEACON study showed that the combination of [cetuximab] and encorafenib significantly improved overall survival in patients with metastatic colorectal cancer with a BRAF V600E mutation – a subtype that typically has worse outcomes compared to those without the mutation," David Hyman, MD, chief medical officer, oncology at Lilly, stated in a press release. "We are grateful to Pfizer for their collaboration as we've worked to bring this treatment regimen to patients."
The active-controlled, open-label, multicenter phase 3 trial enrolled patients with BRAF V600E–mutated metastatic CRC who had progressed after 1 or 2 prior treatment regimens.
Study participants were randomized 1:1:1 to receive oral encorafenib at a once-daily dose of 300 mg plus cetuximab (n = 220), oral encorafenib at a once-daily dose of 300 mg plus cetuximab and binimetinib, or irinotecan with cetuximab or FOLFIRI with cetuximab (n = 221; control arm).
The primary end point of the trial was OS, with additional efficacy outcome measures comprising BICR-assessed PFS, ORR, and DOR. OS and PFS was evaluated in all randomized patients. ORR and DOR was evaluated in a subset of the first 220 patients included in the randomized portion of the encorafenib/cetuximab and control arm of the trial.
Safety was evaluated in a total of 216 patients with BRAF V600E–mutated metastatic CRC who received cetuximab at an initial infusion of 400 mg/m2, followed by a weekly dose of 250 mg/m2 plus encorafenib at a once-daily dose of 300 mg.
The adverse effects that were most frequently reported in those who received encorafenib plus cetuximab included fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.
The label for cetuximab includes warning and precautions regarding infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia and accompanying electrolyte abnormalities, and embryo-fetal toxicity.
Previously, in April 2020, the FDA approved encorafenib for this indication based on data from BEACON CRC.2