ASCO 2015 Report: Dual immunotherapy improves progression-free survival in advanced melanoma

by Bruce Sylvester: Treatment of advanced melanoma with a combination of  nivolumab (Opdivo™) and ipilimumab (Yervoy™) or with nivolumab alone increases progression-free survival over ipilimumab monotherapy, researchers reported on May 31, 2015 at the American Society of Clinical Oncology (ASCO) annual meeting and published online simultaneously in the New England Journal of Medicine (NEJM).

“We’re very encouraged that the initial observations about the efficacy of this combination held up in this large phase III trial,” said lead investigator Jedd Wolchok, MD, PhD, Chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York, NY

In this phase III trial, investigators randomized 945 subjects with untreated advanced melanoma to receive ipilimumab alone, nivolumab alone, or a combination of both.

Patients receiving combination therapy achieved a median progression-free survival of 11.5 months. Median progression-free survival for nivolumab monotherapy subjects  was 6.9 months and 2.9 months for ipilimumab monotherapy.

The researchers reported that 57.6 percent of the 314 subjects on combination therapy achieved an objective response, measured as a significant reduction in tumor size, compared to 43.7 percent of the 316 receiving nivolumab alone and 19 percent of the 315 receiving ipilimumab alone.

Subjects with tumors expressing PD-L1 achieved a median progression-free survival of 14 months, whether they received the combination or nivolumab monotherapy. For subjects not expressing PD-L1, median PFS was 11.2 months on combination therapy and 5.3 months on nivolumab monotherapy.

“One of the biggest questions in the field of immunotherapy has been how to determine which patients will respond to immune-modulating drugs. Now we have another piece of data,” said Wolchok. “A simple pathology test can identify patients whose tumors express PD-L1, and this information will help the patient and physician decide whether to use the combination or nivolumab alone, knowing the toxicity risks and the difference in PFS. However, if a patient’s tumor does not express PD-L1, the data suggests it makes more sense to offer the combination. This understanding gets us closer to ‘precision immunotherapy.'”

Notably, diarrhea and increased lipase occurred in 55 percent of combination therapy subjects, and this led to about one-third of these patients stopping dual therapy. About 16 percent of patients receiving nivolumab monotherapy and 27 percent of patients receiving ipilimumab monotherapy reported side effects, with about 8 percent and 15 percent of the subjects discontinuing, respectively.

ASCO expert commentator Steven O’Day, MD, oncologist, director of The Los Angeles Skin Cancer Institute and director of Clinical Research at The Beverly Hills Cancer Institute in Beverly Hills, CA. “Immunotherapy drugs have already revolutionized melanoma treatment, and now we’re seeing how they might be even more powerful when they’re combined. But the results also warrant caution – the nivolumab and ipilimumab combination used in this study came with greater side effects, which might offset its benefits for some patients. Physicians and patients will need to weigh these considerations carefully.”

The study received funding from Bristol-Myers Squibb.