FDA Approves Nivolumab plus Ipilimumab, Chemotherapy for Metastatic NSCLC

The Food and Drug Administration (FDA) approved the combination of nivolumab (OPDIVO, Bristol-Myers Squibb) plus ipilimumab (YERVOY, Bristol-Myers Squibb) and 2 cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

Efficacy was investigated in CHECKMATE-9LA, a randomized, open-label trial in patients with metastatic or recurrent NSCLC. Patients were randomized to receive either the combination of nivolumab plus ipilimumab and 2 cycles of platinum-doublet chemotherapy (n=361) or platinum-doublet chemotherapy for 4 cycles (n=358).

The trial demonstrated a statistically significant benefit in overall survival (OS) for patients treated with nivolumab plus ipilimumab plus chemotherapy compared to those who received chemotherapy. Median OS was 14.1 months (95% CI: 13.2, 16.2) versus 10.7 months (95% CI: 9.5, 12.5), HR 0.69; 96.71% CI: 0.55, 0.87).

Median progression-free survival (PFS) per blinded independent central review (BICR) was 6.8 months (95% CI: 5.6, 7.7) in the nivolumab plus ipilimumab and chemotherapy arm and 5 months (95% CI: 4.3, 5.6) in the chemotherapy arm (HR 0.70; 95% CI: 0.57, 0.86). Confirmed overall response rate (ORR) per BICR was 38% (95% CI: 33, 43) and 25% (95% CI: 21, 30) respectively. Median response duration was 10 months in the nivolumab plus ipilimumab and chemotherapy arm, and 5.1 months in the chemotherapy arm.

The most common adverse reactions in ≥20% of patients receiving nivolumab in combination with ipilimumab and platinum-doublet chemotherapy were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.

The recommended nivolumab dose for this indication is 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy. The nivolumab and ipilimumab is continued until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression.