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FDA expands approval of Opdivo plus Yervoy for melanoma
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The FDA expanded the approval of nivolumab plus ipilimumab to include all patients with unresectable or metastatic melanoma, regardless of BRAF V600 mutational status.
Until now, the combination only had been indicated for patients with BRAF V600 wild-type disease.
Nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) is the only FDA-approved combination of immune checkpoint inhibitors.
Jedd D. Wolchok
“Patients with metastatic melanoma historically have a very challenging disease,” Jedd D. Wolchok, MD, PhD, chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center and a HemOnc Today Editorial Board member, said in a press release. “Recent advances in our understanding of the immune response to cancer has yielded therapies which provide meaningful responses and hope.
“The combination of two immuno-oncology treatments, nivolumab and ipilimumab, has been shown to provide these patients with a much needed improvement in progression-free survival and response rates,” Wolchok added. “This expanded approval for the nivolumab and ipilimumab regimen provides more advanced melanoma patients with an immuno-oncology combination treatment, and the potential for improved outcomes.”
Nivolumab and ipilimumab that target separate but complementary checkpoint pathways. Ipilimumab’s blockade of CTLA-4 augments T-cell activation and proliferation, whereas nivolumab — a PD-1 inhibitor — helps to restore active T-cell response directed at the tumor.
The FDA based the expanded approval on results of the randomized, phase 3 CheckMate 067 trial, which included 945 patients with previously untreated advanced melanoma.
Researchers assigned 314 patients to nivolumab plus ipilimumab, 316 patients to nivolumab monotherapy and 315 patients to ipilimumab monotherapy.
Treatment continued until disease progression or unacceptable toxicity. OS and PFS served as co-primary endpoints.
Preliminary results showed patients assigned the combination or nivolumab monotherapy demonstrated a statistically significant improvement in PFS (P < .0001 for both) compared with those assigned ipilimumab alone.
Researchers reported median PFS of 11.5 months (95% CI, 8.9-16.7) in the combination group, 6.9 months (95% CI, 4.3-9.5) in the nivolumab monotherapy group and 2.9 months (95% CI, 2.8-3.4) in the ipilimumab monotherapy group.
Researchers determined the combination conferred a 58% reduction in risk for progression vs. ipilimumab (HR = 0.42; 95% CI, 0.34-0.51), whereas nivolumab monotherapy conferred a 43% reduction in risk for progression vs. ipilimumab monotherapy (HR = 0.57; 95% CI, 0.47-0.69).
Results also showed a higher rate of confirmed objective response in the combination group (50%) and nivolumab monotherapy group (40%) than the ipilimumab monotherapy group (14%; P < .0001).
Among responders, 76% of those assigned the combination experienced an ongoing response for at least 6 months, compared with 74% of those assigned nivolumab monotherapy and 63% of those assigned ipilimumab monotherapy.
Patients assigned the combination appeared more likely than those assigned nivolumab monotherapy to experience serious adverse reactions (73% vs. 37%), grade 3 or grade 4 adverse reactions (72% vs. 44%), adverse reactions that led to treatment discontinuation (43% vs. 14%) or adverse reactions that led to dosing delays (55% vs. 28%).
The most common adverse reactions were fatigue (59% for combination vs. 53% for nivolumab monotherapy), rash (53% vs. 40%), diarrhea (52% vs. 31%) and nausea (40% vs. 28%). The most frequent serious adverse reactions were diarrhea (13% for combination vs. 2.6% for nivolumab monotherapy), colitis (10% vs. 1.6%) and pyrexia (10% vs. 0.6%).
“The melanoma community is excited to see the ongoing developments in research from the pharmaceutical industry,” Tim Turnham, executive director of the Melanoma Research Foundation, said in a press release. “[This] expanded approvals continue to bring new treatment options to patients, and demonstrate the ongoing impact of immuno-oncology research.”