Phase 3 Trial Results Support Nivolumab Over Ipilimumab for High-Risk Melanoma

A phase 3 trial in patients with advanced melanoma found that nivolumab (Opdivo) outperformed ipilimumab (Yervoy) in terms of recurrence-free survival.

The CheckMate-238 trial, which is still ongoing, randomly assigned 906 patients with melanoma to receive either nivolumab or ipilimumab for up to 1 year. Participants had previously undergone complete resection of stage IIIb/c or stage IV melanoma, putting them at high risk of recurrence. The primary endpoint, recurrence-free survival, was determined by the time from randomization to the first recurrence or death.

According to a press release from Bristol-Myers Squibb (BMS), the manufacturer of both drugs, the group receiving nivolumab showed better recurrence-free survival compared with the ipgroup. Although the statement did not specify the size of the difference between the 2 treatment arms, it indicated that researchers would seek to present the findings at a medical conference.

“These topline results support the potential promise of Opdivo as a treatment option for patients with high-risk surgically resected melanoma. There remains an unmet need for additional options as the majority of stage III and resected stage IV high-risk melanoma patients experience disease recurrence after surgery,” said Vicki Goodman, MD, development lead of Melanoma and Genitourinary Cancers at BMS, in the statement. “We are committed to researching therapies that may better meet the needs of this patient population and look forward to sharing these data with health authorities soon.”

Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, was delivered intravenously every 2 weeks during the trial. Ipilimumab, an immuno-oncology (IO) drug that targets cytotoxic T-lymphocyte antigen 4, was also administered intravenously, but at longer intervals. The press release from BMS notes that patients can develop severe, potentially fatal immune-mediated adverse events while taking ipilimumab.

A combination of the 2 agents has already received accelerated approval for the treatment of unresectable or metastatic melanoma, making it the first IO combination therapy approved for treating metastatic melanoma. On its own, nivolumab is also indicated for some types of unresectable or metastatic melanomas, as well as for treating cancers like metastatic non-small cell lung cancer or advanced renal cell carcinoma.

In the press release, BMS emphasizes that it views IO as a promising avenue for treating cancers that are difficult to manage with traditional therapies.

“Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients,” it stated. “We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents.”

Analysts predicted that the trial findings could boost sales of nivolumab by as much as $1 billion as oncologists choose it over the more toxic ipilimumab, which will help it compete against Merck’s pembrolizumab (Keytruda), another PD-1 inhibitor.