In the phase IIIb CheckMate 401 trial reported in the Journal of Clinical Oncology, Dummer et al described outcomes with first-line nivolumab/ipilimumab followed by nivolumab in a clinically diverse population of patients with unresectable stage III or IV melanoma, including patients with a poorer performance status, brain metastases, and different melanoma subtypes.
In the European-Australian trial, 533 patients enrolled received nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg once every 3 weeks for four doses, followed by nivolumab at 3 mg/kg (240 mg following protocol amendment) once every 2 weeks for up to 24 months. Among the patients, 68% had cutaneous melanoma; 20% had ocular/uveal, mucosal, or acral melanoma; 10% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2; and 8% had brain metastases (5% previously treated, 3% untreated). The primary outcome measure was incidence of grade ≥ 3 select treatment-related adverse events; overall survival was a secondary outcome measure.
Grade ≥ 3 select treatment-related adverse events among all patients included gastrointestinal events in 16%, hepatic events in 15%, endocrine events in 11%, skin events in 7%, renal events in 2%, and pulmonary events in 1%. Incidence rates were similar across patient subgroups. Gastrointestinal (14%) and hepatic (9%) events were the most common causes of treatment discontinuation due to select treatment-related adverse events. Grade 5 events occurred in two patients; one with acute kidney injury and one with colitis. The most common any-grade treatment-related adverse events were diarrhea (35%), pruritus (25%), and fatigue (25%); grade 3 or 4 treatment-related adverse events occurred in 60% of patients, most commonly, elevated lipase (8%), diarrhea (7%), and colitis (6%). Median follow-up for overall survival was 21.6 months. Overall survival at 24 months was 63% in the entire population. By melanoma subgroup, 24-month overall survival was 71% in the cutaneous group, 36% in the ocular/uveal group, 38% in the mucosal group, and 47% in the acral group. Overall survival at 24 months was 44% among patients with cutaneous melanoma and a performance score of 2, and 71% in the brain metastasis group.