Nivolumab/Ipilimumab Continues Improved Outcomes in Advanced Melanoma

June 16, 2016

A combination of the checkpoint inhibitors nivolumab and ipilimumab continues to demonstrate superior clinical activity vs ipilimumab monotherapy in treatment-naive patients with advanced melanoma.

[[{"type":"media","view_mode":"media_crop","fid":"49519","attributes":{"alt":"Image © Nathalie Speliers Ufermann / Shutterstock.com","class":"media-image","id":"media_crop_8017484113124","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5993","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","title":"Image © Nathalie Speliers Ufermann / Shutterstock.com","typeof":"foaf:Image"}}]] A combination of the checkpoint inhibitors nivolumab and ipilimumab continues to demonstrate superior clinical activity vs ipilimumab monotherapy in treatment-naive patients with advanced melanoma, according to a study (abstract 9505) presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.

In the phase III CheckMate 067 trial, the anti–programmed death 1 agent nivolumab plus the anti-CTLA–4 agent ipilimumab significantly improved progression-free survival (PFS) and objective response rate (ORR) vs ipilimumab alone in patients with melanoma. Lead author Jedd Wolchok, MD, PhD, of the Memorial Sloan Kettering Cancer Center in New York, presented updated efficacy and safety results from this study.

The study included 945 treatment-naive patients who received either nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks for 4 doses (followed by nivolumab 3 mg/kg every 2 weeks); nivolumab 3 mg/kg every 2 weeks plus placebo; or ipilimumab 3 mg/kg every 3 weeks for 4 doses plus placebo, until progression or unacceptable toxicity.

With a minimum follow-up of 18 months and median follow-up of 20.7 months, median PFS continued to be significantly longer for nivolumab plus ipilimumab and nivolumab as compared to ipilimumab. “The reduction in risk of progression or death was 45% for nivolumab and 58% for the combination group. In a descriptive analysis the risk of progression for the combination was reduced by 24% when compared to nivolumab alone,” said Wolchok.

The median PFS was 11.5 months for the combination, 6.9 months for nivolumab, and 2.9 months for ipilimumab.

Median duration of response in nivolumab plus ipilimumab responders has not been reached, and was 22.3 months in the nivolumab group and 14.4 months in ipilimumab responders.

About three-quarters of patients receiving nivolumab in combination or alone have ongoing responses as compared to about half of those on ipilimumab alone.

For the nivolumab plus ipilimumab, nivolumab, and ipilimumab groups, median PFS was 15.5, 5.6, and 4 months in patients with a BRAF mutation and 11.3, 7.1, and 2.8 months in BRAF wild-type patients, respectively.

Median PFS by less than 5% PD-L1 tumor expression was 11.1 months with nivolumab plus ipilimumab, 5.3 months for nivolumab alone, and 2.8 months for ipilimumab. Median PFS rates for patients with more than 5% PD-L1 tumor expression were not reached for the combination, 22 months for nivolumab, and 3.9 months for ipilimumab.

Safety data were consistent with earlier reports, with the frequency and types of drug-related grade 3/4 adverse events being 56.5% with nivolumab plus ipilimumab, 19.8% with nivolumab, and 27% with ipilimumab. There were no new toxicities or safety signals, and no treatment-related deaths with the combination.

In conclusion, Wolchok said: “Nivolumab plus ipilimumab and nivolumab alone improved PFS and ORR vs ipilimumab alone in patients with untreated advanced melanoma. In descriptive analyses, the combination resulted in numerically greater PFS and ORR than nivolumab alone, including in patients with poor prognostic factors. Nivolumab plus ipilimumab resulted in clinically meaningful improvements in ORR regardless of PD-L1 expression. The majority of treatment-related adverse events resolved with immune-modulating medications.”

Results of ongoing survival analyses will further characterize the benefit-risk profile of nivolumab plus ipilimumab and nivolumab alone, he said.