The Food and Drug Administration has approved the immune checkpoint inhibitor nivolumab for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.
The FDA based its approval on an improvement in overall survival demonstrated in CheckMate-141, a randomized trial comparing nivolumab with the investigator’s choice of standard therapy, the FDA said in a written statement .
CheckMate-141 was stopped early in January 2016 after the study met its primary endpoint of improved overall survival in SCCHN patients receiving nivolumab after platinum-based therapy, compared with the investigator’s choice of chemotherapy (methotrexate, docetaxel, or cetuximab).
Earlier this year, the FDA granted accelerated approval to another checkpoint inhibitor targeting the PD-1/PD-L1 pathway, pembrolizumab, for the same indication, based on an objective response rate of 16% in the nonrandomized KEYNOTE-012 trial. Merck Sharp & Dohme, maker of pembrolizumab, is looking to demonstrate an improvement in overall survival with the ongoing KEYNOTE-040 study.
Checkmate-141 enrolled 361 patients with recurrent or metastatic SCCHN with disease progression on or within 6 months of receiving platinum-based chemotherapy and randomized (2:1) to nivolumab 3 mg/kg every 2 weeks intravenously or the investigator’s choice of cetuximab 400 mg/m2 IV once, then 250 mg/m2 IV weekly; methotrexate 40 mg/m2 IV weekly; or docetaxel 30 mg/m2 IV weekly until disease progression or unacceptable toxicity.
As reported at the European Society of Medical Oncology Congress and in the New England Journal of Medicine ( 2016;375:1856-67 ), the median overall survival was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard chemotherapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively.
Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy. The most frequent serious adverse reactions reported in at least 2% of patients receiving nivolumab were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.
The most common adverse reactions occurring in more than 10% of nivolumab-treated patients and at a higher incidence than with standard therapy were cough and dyspnea. The most common laboratory abnormalities occurring in 10% or more nivolumab-treated patients and at a higher incidence than with standard therapy were increased alkaline phosphatase level, increased amylase level, hypercalcemia, hyperkalemia, and increased thyroid-stimulating hormone level, the FDA said.
Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and previously has been approved to treat classical Hodgkin’s lymphoma, advanced renal cell carcinoma, lung cancer, and melanoma.
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