On October 13, 2023, the FDA approved a new indication for nivolumab (Opdivo; Bristol-Myers Squibb Company), a PD-1 inhibitor, for the adjuvant treatment of completely resected stage IIB/C melanoma in patients aged ≥12 years. The FDA granted this application an orphan drug designation.
Nivolumab has been previously approved for the treatment of many cancers, including the adjuvant treatment of melanoma with lymph node involvement or metastatic melanoma in patients who underwent complete resection.
This approval of nivolumab was supported by efficacy findings in the CheckMate76K clinical trial (NCT04099251), a randomized, placebo-controlled, double-blind study that enrolled 790 patients with stage IIB/C melanoma. The patients were randomized (2:1) to nivolumab 480 mg or to placebo dosed via intravenous infusion every 4 weeks for up to 1 year or until disease recurrence or unacceptable adverse events. The patients in this trial underwent complete resection of the primary melanoma with negative margins and a negative sentinel lymph node within 12 weeks before randomization. Randomization was stratified by T category according to the American Joint Committee on Cancer Cancer Staging Manual, 8th Edition (T3b vs T4a vs T4b).
The primary efficacy measure in CheckMate76K was recurrence-free survival (RFS), which was defined as the investigator-assessed time between randomization and first disease recurrence (local, regional, or distant metastasis), new primary melanoma, or death from any cause, whichever occurred first. The median RFS was not reached in the nivolumab arm (95% confidence interval [CI], 28.5-not reached) or in the placebo arm (95% CI, 21.6-not reached) (hazard ratio [HR], 0.42; 95% CI, 0.30-0.59; P≤.0001). At 1 year, the RFS rate was 89% (95% CI, 86-92) for nivolumab compared with 79% (95% CI, 74-84) for placebo. In a prespecified exploratory subgroup analysis, the RFS unstratified HR was 0.34 (95% CI, 0.20-0.56) in patients with stage IIB melanoma and 0.51 (95% CI, 0.32-0.81) in patients with stage IIC melanoma.
The most common (≥20%) adverse events with nivolumab treatment in CheckMate76K were fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.
“Following surgical removal of melanoma, patients may believe they are free of disease. However, within 5 years of diagnosis, one-third of patients with surgically resected stage IIB and nearly one-half of patients with surgically resected IIC melanoma see their cancer return, underscoring the need for additional treatment options that may help reduce the risk of cancer coming back. The significant recurrence-free survival improvement observed with nivolumab in CheckMate-76K is an important step forward for these patients,” stated John M. Kirkwood, MD, Distinguished Professor of Medicine at the University of Pittsburgh School of Medicine, and Co-Director of the Melanoma Center at UPMC Hillman Cancer Center, in a press release.
The recommended dose of nivolumab for patients weighing ≥40 kg is 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable adverse events for up to 1 year. The recommended dose for pediatric patients weighing <40 kg is 3 mg/kg nivolumab every 2 weeks or 6 mg/kg every 4 weeks until disease progression or unacceptable adverse events for up to 1 year.