On October 13, 2023, nivolumab was approved for adjuvant treatment of completely resected stage IIB/C melanoma in patients aged 12 years and older.¹

Supporting Efficacy Data

Approval was based on findings in the double-blind CheckMate 76K trial (ClinicalTrials.gov identifier NCT04099251), in which 790 patients were randomly assigned on a 2:1 basis to receive nivolumab at 480 mg (n = 526) or placebo (n = 264) every 4 weeks for up to 1 year or until recurrence or unacceptable toxicity. Patients had to have complete resection of the primary melanoma with negative margins and a negative sentinel lymph node within 12 weeks prior to randomization.

Median recurrence-free survival was not reached in either the nivolumab group (95% confidence interval [CI] = 28.5 months to not reached) or placebo group (95% CI = 21.6 months to not reached). Recurrence-free survival events occurred in 13% vs 26% of patients (hazard ratio = 0.42, 95% CI = 0.30–0.59, P < .0001), respectively.

How It Is Used

The recommended dose of nivolumab is 240 mg every 2 weeks or 480 mg every 4 weeks in patients ≥ 40 kg and 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks in those < 40 kg, with treatment continuing until disease progression or unacceptable toxicity or for up to 1 year.

No dose reduction is recommended. In general, nivolumab should be withheld for grade 3 immune-mediated adverse reactions and discontinued for grade 4 reactions and recurrent grade 3 reactions that require systemic immunosuppressive treatment or an inability to reduce corticosteroid dose to ≤ 10 mg prednisone or equivalent per day within 12 weeks of initiating steroids.

Safety Profile

In CheckMate 76K, the most common adverse events of any grade among patients receiving nivolumab were fatigue (36% vs 34% in the placebo group), musculoskeletal pain (30% vs 26%), rash (28% vs 15%), diarrhea (23% vs 16%), and pruritus (20% vs 11%). The most common grade 3 or 4 adverse events included diarrhea (1.3%) and rash (1.1%). The most common grade 3 or 4 laboratory abnormalities were increased lipase (2.9%), aspartate aminotransferase (2.2%), and alanine aminotransferase (2.1%).

Nivolumab has warnings/precautions for immune-mediated reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving nivolumab. 

REFERENCE

1. Opdivo (nivolumab), Bristol Myers Squibb, October 2023. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2023/125554Orig1s121lbl.pdf. Accessed October 31, 2023.