MELANOMA – In a double-blind trial, 945 patients with previously untreated, unresectable stage III or IV melanoma were randomized to receive ipilimumab, nivolumab, or combination therapy with ipilimumab and nivolumab. Progression-free survival, a primary endpoint, improved by 43% with nivolumab (median 6.9 months) and by 58% with combination therapy (median 11.5 months), compared to ipilimumab (median 2.9 months). In patients with tumors that expressed the programmed death ligand 1 (PD-L1) on ≥5% of cells, median progression-free survival was similar in the nivolumab and combination groups (both 14.0 months); in those with tumors that expressed PD-L1 on <5% of cells, it was 5.3 months with nivolumab alone and 11.2 months with both drugs. Rates of complete or partial response were 19.0% with ipilimumab, 43.7% with nivolumab, and 57.6% with combination therapy. At least one severe (grade 3-4) drug-related adverse effect occurred in 27.3% of patients receiving ipilimumab, 16.3% of those receiving nivolumab, and 55.0% of those receiving both drugs.2

NONSQUAMOUS NSCLC – In an open-label trial (available only as an abstract), 582 patients with advanced nonsquamous NSCLC that had progressed during or after treatment with a platinum doublet-based regimen (and, if appropriate, a kinase inhibitor) were randomized to receive nivolumab or docetaxel until disease progression or unacceptable toxicity occurred. Nivolumab significantly improved overall survival, the primary endpoint, by 27% compared to docetaxel (median 12.2 vs 9.4 months). Survival rates in the two groups were similar in patients with tumors expressing PD-L1 on <1% of cells, but in patients with tumors expressing PD-L1 on ≥1%, ≥5%, and ≥10% of cells, nivolumab improved overall survival by 41%, 57%, and 60%, respectively, compared to docetaxel. Patients receiving nivolumab were significantly more likely to have an objective response (19.2% vs 12.4%). Severe (grade 3+) drug-related adverse effects occurred in 10.5% of patients receiving nivolumab and in 53.7% of those receiving docetaxel.3