Nivolumab for Adjuvant Treatment of Melanoma Granted Regular Approval by FDA

On December 20, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to the anti–programmed cell death protein 1 (PD-1) monoclonal antibody nivolumab (Opdivo) for the adjuvant treatment of patients with melanoma with involvement of lymph nodes, or in patients with metastatic disease who have undergone complete resection.

Nivolumab was previously approved for the treatment of patients with unresectable or metastatic melanoma.

CheckMate 238

Approval was based on improvement in recurrence-free survival in the randomized, double-blind CheckMate 238 trial. In the trial, 906 patients with completely resected, stage IIIB/C or stage IV melanoma were randomly allocated (1:1) to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab (Yervoy) 10 mg/kg every 3 weeks for 4 doses, then every 12 weeks beginning at week 24 for up to 1 year. Enrollment required complete resection of melanoma with margins negative for disease within 12 weeks prior to randomization.

The major efficacy outcome measure was recurrence-free survival, defined as the time between the randomization date and the date of first recurrence (local, regional, or distant metastasis), new primary melanoma, or death from any cause—whichever occurred first.

Patients in the nivolumab arm experienced fewer recurrences/deaths, 34% (n =154), compared with 45.5% (n = 206) in the ipilimumab arm (hazard ratio = 0.65; 95% confidence interval = 0.53–0.80; P < .0001). Median recurrence-free survival was not reached on either arm.

The median duration of nivolumab exposure was 11.5 months, and 74% of patients received nivolumab for greater than 6 months. Nivolumab was discontinued for adverse reactions in 9% of patients.

The most common adverse reactions (reported in at least 20% of nivolumab-treated patients in CheckMate 238) were fatigue, diarrhea, rash, musculoskeletal pain, pruritus, headache, nausea, upper respiratory infection, and abdominal pain. The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%).

The recommended dose and schedule of nivolumab in adjuvant melanoma is 240 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease recurrence or unacceptable toxicity, for a maximum of 1 year.

Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125554lbl.pdf.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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