FDA Approves BMS's Opdivo as Adjuvant Therapy in Patients with Completely Resected Melanoma with Lymph Node Involvement or Metastatic Disease

The FDA has approved Bristol-Myers Squibb Company's Opdivo (nivolumab) injection for intravenous use for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. The purpose of adjuvant therapy is to reduce the risk of recurrence following surgical removal of the tumor and lymph nodes that contain cancer. In the Phase 3 CheckMate -238 trial, Opdivo significantly improved recurrence-free survival (RFS) versus an active comparator, Yervoy (ipilimumab), in patients with stage IIIB/C or stage IV melanoma after surgery. This benefit was observed across important subgroups, including in both BRAF mutant and BRAF wild-type patients. Opdivo is the first agent approved for the adjuvant treatment of melanoma based on a head-to-head trial against an active comparator with a proven overall survival benefit.

“Today’s approval builds on our leadership in melanoma, offering physicians a new option with the potential to change the course of the disease through earlier intervention. Opdivo is the first PD-1 inhibitor approved as an adjuvant treatment for any cancer,” said Johanna Mercier, head, US Commercial, Bristol-Myers Squibb. “Our decision to study Opdivo versus Yervoy—an established standard of care with a proven survival benefit—represents our relentless pursuit to bring more effective treatments to patients.”

In the CheckMate -238 clinical trial, Opdivo demonstrated an 18-month RFS rate of 66.4 percent compared with 52.7 percent for Yervoy, with the median RFS not yet reached in either group.Opdivo reduced the risk of disease recurrence by 35 percent versus Yervoy.

Opdivo received Breakthrough Therapy Designation from the FDA for the adjuvant treatment of patients with high-risk, fully resected melanoma in September 2017. Approximately three in every 10 patients with stage III melanoma currently receive adjuvant therapy after surgery. Even with available treatment options, the majority of stage IIIB and IIIC melanoma patients (71 and 85 percent, respectively) experience disease recurrence within five years.

Opdivo is the first programmed death-1 (PD-1) immune checkpoint inhibitor to demonstrate superiority, including better tolerability, versus Yervoy,a standard of care in this patient population. Based on data from the CheckMate -238 trial, the National Comprehensive Cancer Network (NCCN) 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.

In CheckMate -238, adverse events (AEs) leading to discontinuation were reported in nine percent of Opdivo-treated patients (n=44/452) and in 42 percent of Yervoy-treated patients (n=193/453). Adverse reactions leading to one or more omitted doses occurred in 28 percent of patients who received Opdivo. Grade 3 or 4 AEs were experienced by 25 percent of patients (n=115/452) in the Opdivo group and 55 percnt of patients (n=250/453) in the Yervoy group. Serious adverse reactions occurred in 18 percent of patients treated with Opdivo.

“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 NYU Langone Health, and Professor of Medicine at NYU School of Medicine. “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. 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.”

Bristol-Myers Squibb pioneered the use of immune checkpoint inhibitors for the adjuvant treatment of melanoma, beginning with Yervoy. Five-year overall survival data from the Phase 3 CA184-029 trial were recently added to the prescribing information for Yervoy for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1mm who have undergone complete resection, including total lymphadenectomy. In the trial, 65 percent of patients treated with Yervoy were alive at five years, compared with 54 percent of patients who received placebo. This analysis was conducted at a median follow-up of 5.3 years.

“Although there are approved therapies to help prevent melanoma recurrence, around seven out of 10 patients with stage III disease do not receive treatment following surgery,” said Valerie Guild, co-founder and president, AIM at Melanoma Foundation. “As an advocate, I have witnessed countless times the frustration and fear patients experience when their cancer returns – even after it was removed by surgery. Today’s approval offers new hope for people with melanoma that their disease may not come back.”