Background
Phase 3, open-label RCT (MAPS; IFCT-0701). 448 patients with unresectable malignant pleural mesothelioma (MPM), no prior chemotherapy, ECOG PS 0–2. Tested whether adding bevacizumab (anti-VEGF) to standard pemetrexed-cisplatin improves survival.
Interventions and follow up
Arm A: Pemetrexed 500 mg/m² + cisplatin 75 mg/m² + bevacizumab 15 mg/kg q21d × 6 cycles, then bevacizumab maintenance until progression/toxicity.
Arm B: Pemetrexed + cisplatin × 6 cycles (no maintenance).
Primary endpoint: Overall survival
mFollow up: 39.4mo
Arm B: Pemetrexed + cisplatin × 6 cycles (no maintenance).
Primary endpoint: Overall survival
mFollow up: 39.4mo
Results
OS: 18.8 vs 16.1mo, HR 0.77, 95% CI 0.62–0.95, P=.0167
PFS: 9.2 vs 7.3mo, HR 0.61, 95% CI 0.50–0.75, P<.0001
ORR: 40.1% vs 28.6%, P=.019
DCR: 80.9% vs 68.7%
PFS: 9.2 vs 7.3mo, HR 0.61, 95% CI 0.50–0.75, P<.0001
ORR: 40.1% vs 28.6%, P=.019
DCR: 80.9% vs 68.7%
Adverse events
Vascular (bevacizumab-related): Grade ≥3 hypertension 23% vs 0%; thrombotic events 6% vs 1%; bleeding 4% vs 1%; fistula/perforation 2 patients vs 0. Discontinuation for bevacizumab toxicity 18%.
Constitutional: Grade ≥3 fatigue 9% vs 7%.
Hematologic: Febrile neutropenia and other hematologic toxicities similar between arms.
Constitutional: Grade ≥3 fatigue 9% vs 7%.
Hematologic: Febrile neutropenia and other hematologic toxicities similar between arms.
Conclusions
Adding bevacizumab to pemetrexed-cisplatin significantly improved OS (18.8 vs 16.1mo, HR 0.77) and PFS in unresectable MPM, the first phase 3 trial to improve upon pemetrexed-cisplatin and establishing a new standard for fit patients.
Key Limitations
Open-label design. 2.7-month absolute OS gain is modest. Grade ≥3 hypertension in 23% requires monitoring. Bevacizumab contraindicated with recent hemoptysis, significant cardiovascular disease, or anticoagulation — common in elderly mesothelioma patients. Benefit in PS 2 uncertain. Predates immunotherapy era (CheckMate-743).
Clinical Context
MAPS established bevacizumab + pemetrexed + cisplatin as a standard first-line option for fit unresectable MPM (ESMO guidelines). Nivolumab + ipilimumab (CheckMate-743) later showed OS benefit, especially in non-epithelioid histology (HR 0.46), and is now preferred frontline for many, particularly non-epithelioid. Pemetrexed-platinum remains the backbone for platinum-eligible epithelioid patients not receiving ICI, with bevacizumab as add-on; carboplatin substitutes for cisplatin in renal impairment.