Background
Phase III double-blind placebo-controlled RCT (CONFIRM); N=332; relapsed malignant pleural or peritoneal mesothelioma after ≥2 prior lines; randomized 2:1.
Interventions and follow up
Arm A: Nivolumab 240mg IV Q2W
Arm B: Placebo
Primary endpoints: Investigator-assessed PFS and OS
mFollow up: 5.1mo
Arm B: Placebo
Primary endpoints: Investigator-assessed PFS and OS
mFollow up: 5.1mo
Results
mPFS: 3.0mo vs 1.8mo (A vs B), HR 0.67, 95% CI 0.53-0.85, P=.0012
mOS: 10.2mo vs 6.9mo, HR 0.69, 95% CI 0.52-0.91, P=.0090
mOS: 10.2mo vs 6.9mo, HR 0.69, 95% CI 0.52-0.91, P=.0090
Adverse events
Overall: Grade 3-4 treatment-related events 19% vs 6.3% (A vs B)
Serious AEs: 41% vs 44%
Respiratory: Dyspnoea 8% vs 9%; pneumonia 6% vs 5%; lower respiratory tract infection 4% vs 7%
Discontinuation for toxicity: 13% vs 3%
Serious AEs: 41% vs 44%
Respiratory: Dyspnoea 8% vs 9%; pneumonia 6% vs 5%; lower respiratory tract infection 4% vs 7%
Discontinuation for toxicity: 13% vs 3%
Conclusions
Nivolumab improved PFS and OS vs placebo in relapsed malignant mesothelioma after ≥2 prior lines of chemotherapy, supporting single-agent immunotherapy in the relapsed setting.
Key Limitations
Short follow-up at primary analysis; modest absolute PFS gain (~1mo); PD-L1 not predictive of benefit; conducted before first-line ipi/nivo became standard, shifting the relapsed-line context.
Clinical Context
No specific FDA/EMA approval for nivolumab in relapsed mesothelioma; ESMO recognizes single-agent anti-PD-1 as a relapsed-line option. With first-line ipi/nivo now standard, applicability is greatest for immunotherapy-naïve relapsed patients.