Data from the phase 3 CheckMate-76K trial found that adjuvant nivolumab was effective in improving recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) among patients with completely resected stage IIB/C melanoma.¹ These findings supported the use of nivolumab in adjuvant setting to prevent disease recurrence of stage IIB/C melanoma.¹

The current primary treatment for patients with localized melanoma is surgical excision of the tumor.² However, >10% of patients who had undergone surgical excision would develop recurrent disease.³ For patients with stage II melanoma, only <60% of patients could remain disease-free in 5 years.⁴ As a consequence of disease recurrence, 20% of patients with recurrent disease would experience metastatic disease, having a 5-year overall survival (OS) rate of merely 9%-28%.³ To reduce the risk of disease recurrence of stage II melanoma after surgical treatment, adjuvant therapy is warranted. Nivolumab is a programmed death 1 (PD-1) inhibitor approved for the treatment of multiple malignancies, including unresectable and metastatic melanoma.⁵ In the adjuvant setting, the drug has also shown positive results in prolonging RFS among patients with completely resected stage IIIB, IIIC, and IV melanoma, as reported in CheckMate 238.⁵

The CheckMate76K study was a phase 3, randomized controlled trial that evaluated the efficacy of nivolumab in improving the RFS rate of stage IIB and IIC melanoma patients.¹ The study enrolled treatment-naïve patients aged ≥12 years with completely resected stage IIB or IIC melanoma, and who had a negative sentinel lymph node biopsy.¹ A total of 790 patients were enrolled and randomized 2:1 to receive either nivolumab 480mg intravenously every 4 weeks for 12 months, or placebo.¹ The median follow-up was 15.8 months.¹

In this trial, nivolumab yielded a 58% reduction in the risk of death or disease recurrence compared with the placebo group (HR=0.42, 95% CI: 0.30-0.59, p<0.0001).¹ Improvement in RFS by the nivolumab treatment was maintained across the predefined patient subgroups, regardless of disease stage and T category.¹ At 12 months, the RFS was 89% in the nivolumab group and 79% in the placebo group.¹ The 12-month RFS rate in the stage IIB group was 93% with nivolumab vs. 84% with placebo (T3b: 83%, T4a: 85%); while in the stage IIC group, nivolumab produced an RFS rate of 84% vs. 72% in the placebo group.¹ In addition, nivolumab achieved a DMFS rate of 92% compared with 87% in the placebo group, with a relative risk reduction of 53% (HR=0.47; 95% CI: 0.30-0.72).¹

The safety findings of nivolumab in this trial were consistent with the established safety profile of nivolumab.¹ About 83% of patients in the nivolumab group experienced treatment-related adverse events (TRAEs) of any grade and 10% experienced TRAEs of grade 3-4.¹ In comparison, 54% of patients in the placebo group experienced TRAEs, with 2% experiencing TRAEs of grade 3-4.¹ The most common TRAEs included fatigue, pruritus, diarrhea, rash, and arthralgia.¹

Overall, this study demonstrated the promising efficacy and consistent safety profiles of nivolumab among patients who had completely resected stage IIB or IIC melanoma.¹ The above findings supported the use of nivolumab as an adjuvant treatment option for the prevention of disease recurrence after surgical treatment of stage IIB/C melanoma.¹