Benefits of Adding Bevacizumab to Cisplatin-Pemetrexed in Pleural Mesothelioma
Adding bevacizumab to cisplatin-pemetrexed improves overall survival by 2.7 months (18.8 vs 16.1 months) and should be offered to carefully selected patients under age 75 with good performance status and no cardiovascular contraindications. 1
Survival Benefits
The MAPS trial demonstrated a statistically significant and clinically meaningful survival advantage:
- Median overall survival increased from 16.1 months to 18.8 months (HR 0.77, p=0.0167) 1, 2
- Progression-free survival improved from 7.3 months to 9.2 months (HR 0.61, p<0.001) 1
- The 1-year survival benefit represents a substantial improvement in this aggressive malignancy 1
Both ASCO and the British Thoracic Society recognize this survival benefit as clinically significant, with ASCO providing a moderate-strength, evidence-based recommendation for bevacizumab addition 1
Patient Selection Criteria
Bevacizumab is ONLY appropriate for patients meeting ALL of the following:
- Age ≤75 years 1, 3
- ECOG performance status 0-2 (NOT ≥2) 1, 3
- No substantial cardiovascular comorbidity or history of stroke/TIA 4, 3
- No uncontrolled hypertension 1, 4
- No active bleeding or clotting risk 4, 3
- Not on therapeutic anticoagulation at curative doses 4, 2
The rigorous eligibility criteria in the MAPS trial likely contributed to the superior survival in the control arm (16.1 months) compared to historical controls (12.1 months), emphasizing the importance of careful patient selection 1
Toxicity Profile and Management Requirements
Grade 3-4 adverse events increase from 62% to 71% with bevacizumab addition, requiring intensive monitoring: 1, 4
Cardiovascular Toxicity
- Grade 3+ hypertension occurs in 23-25% of patients (versus 0% without bevacizumab) 4, 5
- Blood pressure monitoring at every visit is mandatory 4
- Antihypertensive management will be required in most patients 4
Thrombotic Complications
- Grade 3-4 thrombotic events increase from 1% to 6% 4, 2
- Includes deep vein thrombosis and intra-abdominal thrombosis 4
Bleeding Events
- Epistaxis occurs in 37.4% of patients (mostly grade 1-2) versus 6.3% without bevacizumab 4, 2
- While usually mild, this is a characteristic bevacizumab side effect requiring patient counseling 4
Renal Toxicity
- Grade 3 proteinuria occurs in 3.1% versus 0% without bevacizumab 4
- Regular urine protein monitoring (dipstick or quantitative) is required 4
Treatment Discontinuation
- Treatment discontinuation due to toxicity increases from 6% to 24.3% in the bevacizumab arm 1, 4
- Despite increased toxicity, quality of life was maintained with no detriment compared to chemotherapy alone 1, 4
Practical Implementation
The recommended regimen is:
- Bevacizumab 15 mg/kg IV every 21 days 1, 2
- Cisplatin 75 mg/m² IV every 21 days 1, 3
- Pemetrexed 500 mg/m² IV every 21 days 1, 3
- Continue for up to 6 cycles, then bevacizumab maintenance until progression 1, 2
Essential supportive care includes:
- Vitamin B12 1000 μg IM starting ≥1 week before first dose, then every 9 weeks 3, 6
- Folic acid 0.4-1.0 mg PO daily starting ≥1 week before first dose 3, 6
Important Caveats
Data for bevacizumab with carboplatin-pemetrexed are insufficient for a clear recommendation 1. A phase II trial showed promising results, but ASCO explicitly states the evidence is inadequate to recommend this combination 1
The recent BEAT-meso trial (2025) evaluated adding atezolizumab to bevacizumab-carboplatin-pemetrexed but failed to meet its primary OS endpoint, though PFS improved 7. This suggests bevacizumab-chemotherapy remains the standard triplet without immunotherapy addition 7
Bevacizumab is not currently licensed for mesothelioma in the UK and is not available through the NHS 1, highlighting access limitations in some healthcare systems.