Background
Phase III open-label RCT (CheckMate 743); N=605; treatment-naïve unresectable malignant pleural mesothelioma; randomized 1:1.
Interventions and follow up
Arm A: Nivolumab 3mg/kg IV Q2W + ipilimumab 1mg/kg IV Q6W up to 2 yr
Arm B: Platinum (cisplatin 75mg/m2 or carboplatin AUC5) + pemetrexed 500mg/m2 Q3W x6
Primary endpoint: Overall survival
mFollow up: 29.7mo
Arm B: Platinum (cisplatin 75mg/m2 or carboplatin AUC5) + pemetrexed 500mg/m2 Q3W x6
Primary endpoint: Overall survival
mFollow up: 29.7mo
Results
mOS, overall: 18.1mo vs 14.1mo (A vs B), HR 0.74, 95% CI 0.60-0.91, P=.0020
mOS, epithelioid: 18.7mo vs 16.5mo, HR 0.86, 95% CI 0.69-1.08
mOS, non-epithelioid: 18.1mo vs 8.8mo, HR 0.46, 95% CI 0.31-0.68
mOS, epithelioid: 18.7mo vs 16.5mo, HR 0.86, 95% CI 0.69-1.08
mOS, non-epithelioid: 18.1mo vs 8.8mo, HR 0.46, 95% CI 0.31-0.68
Adverse events
Overall: Grade ≥3 treatment-related events 30% vs 32% (A vs B)
Most common (arm A): Skin 36%; GI 22%
Treatment-related deaths: 3 (1%) vs 1 (<1%)
Most common (arm A): Skin 36%; GI 22%
Treatment-related deaths: 3 (1%) vs 1 (<1%)
Conclusions
First-line nivolumab + ipilimumab significantly improved OS vs platinum-pemetrexed in unresectable malignant pleural mesothelioma, with the largest benefit in non-epithelioid histology.
Key Limitations
Open-label; epithelioid subgroup (majority) did not reach significant OS separation; no maintenance chemotherapy in control arm; predictive value of PD-L1 limited.
Clinical Context
FDA approved first-line nivolumab + ipilimumab for unresectable malignant pleural mesothelioma (Oct 2020); EMA approved 2021. ESMO endorses ipi/nivo as preferred first-line, particularly for non-epithelioid histology.
References