Recently published long-term survival data shows the benefits of combining two conventional therapies to treat patients with advanced melanoma.
A recent trial demonstrated the therapeutic benefit of combining nivolumab with ipilimumab in advanced melanoma; patients who were treated with this regimen had longer progression-free survival and a higher objective response rate, compared with those who were given ipilimumab alone. However, the 3-year overall survival (OS) data from this trial had yet to be finalized.
Led by Jedd D Wolchok, MD, PhD, Memorial Sloan Kettering Cancer Center (New York, NY), a group of investigators conducted the phase III trial to assess for progression-free survival and OS in patients with advanced melanoma after treatment with various regimens. Patients with previously untreated disease were randomly assigned (1:1:1) to receive any of three options until progression, occurrence of unacceptable toxicity, or withdrawal of consent:
- Nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks
- Nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo
- Ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo
Randomization of the patients was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. Results of the long-term analysis were published in the New England Journal of Medicine (online September 11, 2017; doi:10.1056/NEJMoa1709684).
After a minimum follow-up of 36 months, researchers reported that the median OS had not been reached in the nivolumab plus ipilimumab cohort, was 37.6 months in the nivolumab alone cohort, and was 19.9 months in the ipilimumab alone cohort. Additionally, the OS rate after 3 years was reported highest in the nivolumab plus ipilimumab cohort (58%), compared with the nivolumab alone cohort (52%) and the ipilimumab alone cohort (34%).
Researchers acknowledged that treatment-related adverse events of grade 3/4 were observed in 59% of patients in the nivolumab plus ipilimumab cohort, 21% of patients in the nivolumab alone cohort, and 28% of patients in the ipilimumab alone cohort. The safety profile was comparable to the initial findings from the study, they noted.
Authors of the study concluded that long-term survival outcomes were significantly improved for patients with advanced melanoma after taking a nivolumab plus ipilimumab combination regimen, compared with ipilimumab alone. The study was not designed to compared the nivolumab combination regimen with nivolumab alone, they admitted, and further studies will need to be designed for this purpose.—Zachary Bessette