In a single-institution phase II trial reported in the Journal of Clinical Oncology, Pelster et al found that nivolumab plus ipilimumab produced durable responses and improved survival outcomes in patients with metastatic uveal melanoma.
The trial enrolled 35 patients at The University of Texas MD Anderson Cancer Center between July 2015 and March 2018. Patients received nivolumab at 1 mg/kg and ipilimumab at 3 mg/kg every 3 weeks for a total of four doses, followed by nivolumab maintenance for up to 2 years; nivolumab maintenance was initially given at 3 mg/kg every 2 weeks, with dosing subsequently changed to 480 mg every 4 weeks. In total, 43% of patients had received one or more prior line(s) of therapy. The primary outcome measure was overall response rate on Response Evaluation Criteria in Solid Tumors version 1.1.
Median follow-up was 13.0 months (range = 1.3–43.5 months). Among 33 patients evaluable for response, confirmed responses were observed in 6 patients (18%), including complete response in 1 patient. Stable disease was observed in an additional 11 patients (33%). The median duration of response was 12.1 months (range = 2.8–43.0 months), with three responses ongoing at data cutoff.
Among 27 evaluable patients with liver metastases, 5 (19%) had a partial response and 3 (11%) had stable disease for 6 months or longer. Among six patients with only extrahepatic metastases, one (17%) had complete response and three (50%) had stable disease for six months or longer.
Among all 35 patients, median progression-free survival was 5.5 months (95% confidence interval [CI] = 3.4–9.5 months). Median progression-free survival among patients with liver metastases vs those with only extrahepatic metastases was 12.0 vs 5.5 months (P = .0918).
Median overall survival was 19.1 months (95% CI = 9.6 months–not reached), with a 1-year rate of 56%. No significant difference in overall survival was observed between patients with liver metastases vs those with only extrahepatic metastases.
The investigators noted, “The overall survival with nivolumab and ipilimumab of 19.1 months is notably longer than the 6.8 to 9.6 months reported with single-agent checkpoint inhibition.”
Grade 3 or 4 adverse events occurred in 57% of patients (treatment-related in 40%), with the most common being increased alanine transaminase (ALT; 17%), increased aspartate transaminase (AST; 11%), and diarrhea (9%). The most common adverse events of any grade were diarrhea (60%), increased ALT (49%), increased AST (40%), pruritus (40%), and hypothyroidism (37%). Adverse events led to discontinuation of treatment in 29% of patients. No treatment-related deaths were observed.
The investigators concluded, “The combination regimen of nivolumab plus ipilimumab demonstrates activity in metastatic uveal melanoma, with deep and sustained confirmed responses.”
Meredith S. Pelster, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and The University of Texas MD Anderson High Impact Clinical Research Support Program. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.