Overview of Mesothelioma Treatment

Malignant pleural mesothelioma treatment options include first-line nivolumab + ipilimumab (CheckMate-743) and pemetrexed-based chemotherapy with or without bevacizumab. The dual checkpoint inhibitor combination demonstrated improved overall survival compared to chemotherapy, particularly in non-epithelioid histology. Surgery may be considered in selected early-stage patients.

Treatment Selection

First-Line

  • Nivolumab + Ipilimumab (CheckMate-743) — preferred for non-epithelioid
  • Pemetrexed + cisplatin/carboplatin ± bevacizumab

Second-Line

  • Pemetrexed (if not used first-line)
  • Gemcitabine or vinorelbine

Epidemiology & Impact

Malignant pleural mesothelioma has approximately 2,800 US cases annually, overwhelmingly caused by asbestos exposure with 20-50 year latency. Incidence is declining in the US but rising in developing countries. Median age is 72 with 4:1 male predominance. Prognosis is poor with median survival of 12-18 months.

Molecular Biology & Biomarkers

Mesothelioma is dominated by tumor suppressor loss: BAP1 (60-70%), NF2 (40-50%), CDKN2A (50-70%). Germline BAP1 mutations define a hereditary syndrome. Three histologic subtypes (epithelioid, sarcomatoid, biphasic) have distinct molecular features and prognosis.

Evolving Treatment Landscape

Nivolumab-ipilimumab (CheckMate 743) is first-line standard, replacing cisplatin-pemetrexed. This dual immunotherapy particularly benefits non-epithelioid histology. Cisplatin-pemetrexed with or without bevacizumab remains an option for epithelioid type. Surgery is controversial and limited to experienced centers.

Approved Therapies

Opdivo + Yervoy
nivolumab + ipilimumab
FDA Approved 2020
Indications
First-line treatment of unresectable malignant pleural mesothelioma.
Dosing
Nivolumab 360 mg + ipilimumab 1 mg/kg IV every 3 weeks × 4 doses, then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks.
Evidence
CheckMate 743: Nivo+ipi improved OS vs chemotherapy (18.1 vs 14.1 months, HR 0.74) in treatment-naive MPM. First immunotherapy to show survival benefit in mesothelioma. Now preferred first-line option.
Pivotal Trial
Key Publication
Alimta
pemetrexed
FDA Approved 2004
Indications
In combination with cisplatin for treatment of unresectable malignant pleural mesothelioma.
Dosing
500 mg/m² IV day 1 + cisplatin 75 mg/m² day 1 every 21 days. Requires folic acid and B12 supplementation.
Evidence
Pemetrexed+cisplatin improved OS vs cisplatin alone (12.1 vs 9.3 months). Standard chemotherapy backbone for 15+ years before immunotherapy approval.
Pivotal Trial
Key Publication