In a Spanish phase II trial reported in the Journal of Clinical Oncology, Piulats et al found that nivolumab/ipilimumab produced a “modest” improvement in overall survival vs historical rates achieved with chemotherapy as first-line treatment for patients with metastatic uveal melanoma ineligible for liver resection.

Study Details

Fifty-two patients with progressive M1 disease were enrolled in the multicenter Spanish Multidisciplinary Melanoma Group trial between April 2016 and June 2017. Patients received four courses of nivolumab at 1 mg/kg once every 3 weeks and ipilimumab at 3 mg/kg once every 3 weeks followed by nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In total, 79%, 58%, and 32% of patients had liver M1 disease, extra-liver M1 disease, and elevated lactate dehydrogenase (LDH), respectively. The primary endpoint was 12-month overall survival.

Overall Survival

Overall survival at 12 months was 51.9% (95% confidence interval [CI] = 38.3%–65.5%), with a 24-month rate of 26.4%. Median overall and progression-free survival were 12.7 months and 3.0 months. Median overall survival was 9.2 months, 23.5 months, and 15 months among patients with exclusive liver metastasis, those with exclusive extrahepatic metastasis, and those with both liver and other metastasis (overall P = .146). On multivariate analysis, hazard ratios were 3.5 (P = .046) for overall survival and 6.1 (P = .015) for progression-free survival for patients with LDH ≥ 2.5 upper limit of normal vs normal LDH.

Objective response was observed in six patients (11.5%), including complete response in one. Stable disease was observed in an additional 27 patients (51.9%). Median duration of response was 15.6 months.

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 58% of patients, with the most common being liver toxicity/liver-related events (21%), skin-related events (8%), and fatigue (8%). A total of 30 serious treatment-related adverse events were observed, with the most common being fever (n = 4), liver-related events (n = 3), and diarrhea (n = 3). Treatment-related death occurred due to thyroiditis in one patient and Guillain-Barré syndrome in one patient.

The investigators noted that two meta-analyses of first-line treatment with chemotherapy in this setting showed median overall survival of 9.3 months and 0.91 years.

The investigators concluded: “Nivolumab plus ipilimumab in the first-line setting for metastatic uveal melanoma showed a modest improvement in overall survival over historical benchmarks of chemotherapy, with a manageable toxicity profile.”

José María Piulats, MD, PhD, of the Medical Oncology Department, Catalan Institute of Cancer, Barcelona, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Spanish Multidisciplinary Melanoma Group with support from Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.