Bevacizumab (Avastin) for Mesothelioma

Bevacizumab, marketed as Avastin, is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein that tumors use to stimulate the growth of new blood vessels — a process called angiogenesis. By blocking VEGF, bevacizumab starves tumors of their blood supply, inhibiting growth and enhancing the effectiveness of concurrent chemotherapy. While not FDA-approved specifically for mesothelioma, bevacizumab has demonstrated significant survival benefits in the landmark MAPS trial and is used off-label in combination with standard chemotherapy.¹

Mesothelioma tumors are highly vascular, expressing elevated levels of VEGF that correlate with tumor aggressiveness and poor prognosis. This biological characteristic makes VEGF an attractive therapeutic target. Bevacizumab binds to circulating VEGF and prevents it from interacting with VEGF receptors on endothelial cells, thereby blocking the signaling cascade that promotes new blood vessel formation. Additionally, bevacizumab is believed to normalize existing tumor vasculature, improving the delivery of concurrent chemotherapy drugs to the tumor.²

The MAPS (Mesothelioma Avastin Cisplatin Pemetrexed Study) trial, published in The Lancet in 2016, was a landmark phase III study conducted by the French Intergroup (IFCT). It demonstrated that adding bevacizumab to the standard pemetrexed/cisplatin regimen significantly improved median overall survival from 16.1 months to 18.8 months — a 2.7-month improvement with a 23% reduction in the risk of death. This represented the first time any drug had improved upon the pemetrexed/cisplatin backbone in a randomized phase III setting.¹

Despite these positive results, bevacizumab has not received FDA approval for mesothelioma, partly because the MAPS trial was conducted primarily in European centers and the manufacturer did not pursue a mesothelioma-specific indication. Nevertheless, the triplet regimen of pemetrexed/cisplatin/bevacizumab is recognized in NCCN guidelines and is widely used in clinical practice for patients with good performance status and no contraindications to anti-VEGF therapy.³

Bevacizumab is added to the standard pemetrexed/platinum chemotherapy backbone for mesothelioma:¹

Triplet Regimen (MAPS Protocol)

• Pemetrexed — 500 mg/m² intravenously on Day 1
• Cisplatin — 75 mg/m² intravenously on Day 1
• Bevacizumab — 15 mg/kg intravenously on Day 1
• Cycle length — Every 21 days for up to 6 cycles of chemotherapy
• Maintenance — Bevacizumab continued as maintenance monotherapy every 3 weeks until disease progression or unacceptable toxicity

MAPS Trial Results

The phase III MAPS trial randomized 448 patients with unresectable malignant pleural mesothelioma:¹

• Median overall survival — 18.8 months (triplet) vs. 16.1 months (doublet), HR 0.77
• Median progression-free survival — 9.2 months vs. 7.3 months
• Overall response rate — Similar between arms (~40%)
• Disease control rate — 73.5% vs. 71.6%
• Bevacizumab maintenance — The survival benefit was attributed partly to the maintenance phase, with bevacizumab continuing to suppress angiogenesis after chemotherapy completion

Patient Selection Considerations

Not all mesothelioma patients are candidates for bevacizumab. Contraindications include:³

• Uncontrolled hypertension
• Recent surgery (within 4–6 weeks) due to impaired wound healing
• History of arterial thromboembolic events (stroke, myocardial infarction)
• Significant proteinuria (protein in urine)
• History of bowel perforation or fistula
• Active bleeding or hemoptysis (coughing blood)

The addition of bevacizumab to pemetrexed/cisplatin represents one of the most meaningful survival improvements achieved in mesothelioma chemotherapy:¹

• Survival improvement — A 2.7-month improvement in median overall survival with a 23% reduction in the risk of death, statistically significant in the intent-to-treat population
• Progression-free survival — A 1.9-month improvement, indicating that bevacizumab extends the period before the disease worsens
• Maintenance benefit — Continuing bevacizumab as maintenance therapy after completing chemotherapy provides ongoing disease control
• Subgroup analyses — Benefits were observed across histologic subtypes and performance status categories, though epithelioid histology patients showed the most consistent benefit

Bevacizumab's anti-VEGF mechanism produces a distinct set of side effects related to its impact on blood vessel function throughout the body:³

• Hypertension — The most common side effect, occurring in 20–30% of patients. Blood pressure should be monitored before each infusion and at home. Most cases are manageable with standard antihypertensive medications (ACE inhibitors, ARBs, or calcium channel blockers). Severe or uncontrolled hypertension may require treatment discontinuation
• Proteinuria — Protein leakage into the urine occurs in 15–20% of patients due to VEGF's role in maintaining kidney glomerular integrity. Urine dipstick testing is performed before each cycle. Significant proteinuria (>2g/24hr) may require dose interruption
• Bleeding — Increased bleeding risk includes epistaxis (nosebleeds) in 20–30% of patients (usually mild), as well as more serious hemorrhagic events in rare cases. Patients should report any unusual bleeding, blood in stool, or hemoptysis immediately
• Impaired wound healing — Bevacizumab inhibits the angiogenesis necessary for wound repair. Elective surgery should be avoided during treatment, and bevacizumab should be discontinued at least 4–6 weeks before planned surgical procedures
• Thromboembolic events — Arterial events (stroke, myocardial infarction) and venous thromboembolism (deep vein thrombosis, pulmonary embolism) occur at increased rates. Patients should report sudden leg swelling, chest pain, or neurological symptoms immediately
• Gastrointestinal perforation — A rare (1–2%) but serious complication. Patients should report severe abdominal pain, especially with fever or vomiting, as this requires emergency evaluation
• Fatigue — Commonly reported, though often difficult to distinguish from chemotherapy-related fatigue when used in the triplet regimen