FDA Approved Adjuvant Nivolumab for Melanoma

December 27, 2017

The FDA has approved nivolumab for the adjuvant treatment of melanoma; it showed superiority compared with the standard of care in this patient population.

The US Food and Drug Administration (FDA) has approved nivolumab (Opdivo) for the adjuvant treatment of patients with melanoma and involvement of lymph nodes or metastatic disease who have undergone complete resection. Nivolumab is the first programmed death 1 (PD-1) inhibitor to show superiority compared with the standard of care, ipilimumab, in this patient population.

The new indication was granted based on data from the phase III CheckMate-238 trial, which randomly assigned 906 patients to nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks starting at week 24. The primary endpoint was recurrence-free survival.

The trial showed that nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with stage IIIB/C or stage IV melanoma after surgery. Patients assigned nivolumab had an 18-month recurrence-free survival rate of 66.4% compared with 52.7% for ipilimumab. The median recurrence-free survival was not yet reached in either group.

Overall, treatment with nivolumab resulted in a 35% reduction in risk for disease recurrence compared with ipilimumab (hazard ratio, 0.65; 95% CI, 0.53–0.80; P < .0001). This improvement was seen across several subgroups including in patients with BRAF-mutant and BRAF wild-type disease.

In CheckMate-238, 9% of patients assigned nivolumab experienced adverse events that led to discontinuation compared with 42% of patients assigned ipilimumab. Grade 3/4 events occurred in 25% of patients assigned nivolumab compared with 55% of patients assigned ipilimumab.

Based on data from the CheckMate -238 trial, the National Comprehensive Cancer Network recently added nivolumab to its treatment guidelines for completely resected stage IIIB/C melanoma and completely resected stage III melanoma with clinical satellite or in-transit metastases.

“Immuno-Oncology has transformed the treatment of metastatic melanoma and many other cancers over the last decade, and we are now extending the use of novel agents to help prevent the recurrence of melanoma,” said Jeffrey S. Weber, MD, PhD, deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University Langone Health and professor of medicine at NYU School of Medicine, in a press release.

“When melanoma has been removed surgically, physicians and patients alike sometimes struggle with the idea of further adjuvant treatment because the disease is no longer detectable, even though it may be likely to return,” he explained. “We recognized a need to develop new adjuvant treatments with lower toxicity compared to ipilimumab to help address this challenge. With its impressive efficacy and broad applicability within stage III and IV melanoma, nivolumab has the potential to become the next standard of care in preventing recurrence of melanoma following surgical resection.”