On May 15, 2020, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express programmed cell death ligand 1 (PD-L1) at ≥ 1%, as determined by an FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
The FDA also approved the PD-L1 IHC 28-8 pharmDx as a companion diagnostic device for selecting patients with NSCLC for treatment with nivolumab plus ipilimumab.
CheckMate-227
Efficacy was investigated in CheckMate 227, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy. In part 1a of the trial, 793 patients with PD-L1 tumor expression ≥ 1% were randomly assigned to receive either the combination of nivolumab plus with ipilimumab (n = 396) or platinum doublet chemotherapy (n = 397).
The trial demonstrated a statistically significant improvement in overall survival for patients with PD-L1 tumor expression ≥ 1% receiving nivolumab plus ipilimumab compared to those treated with platinum doublet chemotherapy. Median overall survival was 17.1 months (95% confidence interval [CI] = 15–20.1) vs 14.9 (95% CI = 12.7–16.7) (hazard ratio [HR] = 0.79, 95% CI = 0.67–0.94, P = .0066).
Median progression-free survival per blinded independent central review was 5.1 months (95% CI = 4.1–6.3) in the nivolumab plus ipilimumab arm and 5.6 months (95% CI = 4.6–5.8) in the platinum doublet arm (HR = 0.82, 95% CI = 0.69–0.97). Confirmed overall response rate per blinded independent central review was 36% (95% CI = 31%–41%) and 30% (95% CI = 26%–35%), respectively. Median response duration was 23.2 months in the nivolumab plus ipilimumab arm and 6.2 months in the platinum-doublet chemotherapy arm.
The most common adverse reactions in ≥ 20% of patients receiving the combination of nivolumab plus ipilimumab were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritis, nausea, and hepatitis.
The recommended doses for the combination in patients with metastatic NSCLC are nivolumab at 3 mg/kg every 2 weeks and ipilimumab at 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.
