On October 2, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) as first-line treatment for adult patients with unresectable malignant pleural mesothelioma.
Efficacy was investigated in CheckMate 743, a randomized, open-label trial in patients with unresectable malignant pleural mesothelioma who had received no prior anticancer therapy. Patients were randomly assigned to receive either nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).
The trial demonstrated a statistically significant improvement in overall survival for patients treated with nivolumab plus ipilimumab compared with those who received chemotherapy. Median overall survival was 18.1 months (95% confidence interval [CI] = 16.8–21.5) vs 14.1 months (95% CI = 12.5–16.2) (hazard ratio [HR] = 0.74, 95% CI = 0.61–0.89, P = .002).
Median progression-free survival per blinded independent central review was 6.8 months (95% CI = 5.6–7.4) in the nivolumab plus ipilimumab arm and 7.2 months (95% CI = 6.9–8.1) in the chemotherapy arm (HR = 1.0, 95% CI = 0.82–1.21). Confirmed overall response rate per blinded independent central review was 40% (95% CI = 34–45) and 43% (95% CI = 37–49) in the nivolumab plus ipilimumab and chemotherapy arms, respectively. Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm.
The most common adverse reactions (incidence ≥ 20%) in patients receiving the combination of nivolumab plus ipilimumab in CheckMate 743 were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
The recommended doses for adult patients with unresectable malignant pleural mesothelioma are nivolumab at 360 mg every 3 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.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. FDA approval occurred approximately 5 months ahead of the goal date.