OnCo
cancersCancer

Mesothelioma

An asbestos-caused cancer of the lung lining. Immunotherapy doublets replaced chemotherapy in 2020, and mesothelin CAR-T is under study.

Malignant pleural mesothelioma arises from the lining of the lung, almost always decades after asbestos exposure, and is rising in countries that banned asbestos late or not at all. It grows along surfaces rather than as a mass, is hard to image and stage, and resists most systemic therapy. Histology is the dominant biological variable: epithelioid tumours are slower and chemosensitive; sarcomatoid and biphasic tumours are aggressive, chemoresistant, and paradoxically more immunotherapy-responsive.

For 16 years after pemetrexed-cisplatin (2004) nothing improved survival except, modestly, adding bevacizumab (MAPS, 2016). Immunotherapy then changed the first line twice: nivolumab-ipilimumab (CheckMate 743, approved 2020) and pembrolizumab with chemotherapy (IND.227/KEYNOTE-483, approved September 2024). Tumour treating fields hold a device approval on single-arm data. Radical surgery, long assumed beneficial, was shown by MARS 2 (2024) to shorten survival and worsen quality of life, and is now largely confined to trials.

What comes next is biology-led: PRMT5 and MAT2A inhibitors for the ~40-50% of tumours with MTAP deletion, mesothelin-directed CAR-T delivered into the pleural space, ADCs and T-cell engagers against mesothelin, and better use of histology and BAP1/CDKN2A status to choose therapy. Prevention remains the biggest lever: asbestos is still mined and used in parts of Asia, Russia, and Brazil.

State of the art today

  • IO doublet first line.
  • Two immunotherapy-based first-line standards (nivolumab-ipilimumab; pembrolizumab-chemotherapy), chosen by histology.
  • Radical surgery removed from routine care after MARS 2 showed harm.
  • MTAP deletion and BAP1 loss are routine diagnostic markers and emerging therapeutic handles.
Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Five-year survival with nivolumab-ipilimumab 14% vs 6% with chemotherapy: a small but real tail of long-term survivors.
  • Mesothelin CAR-T delivered regionally has produced long survivors in phase 1.
Who it affects

Incidence is still rising in Asia and parts of Europe because of asbestos exposure 20-50 years ago.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Mesothelioma causes about 30,000 cases a year worldwide, ~3,000 in the US, with median survival of 12-18 months.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Mesothelioma. World: 30,633 new cases, 25,371 deaths.

#CountryNew casesDeaths
1United Kingdom3,2272,664
2United States of America3,1142,435
3China2,3811,681
4Italy2,3371,861
5Japan2,1371,729
6Russian Federation1,7841,636
7Germany1,7711,534
8France (metropolitan)1,6321,243
9India1,6131,432
10Australia961831

Standard of care

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Unresectable

Nivolumab-ipilimumab or chemo-IO; TTFields.

NCCN Guidelines: Mesothelioma (Pleural)
NivolumabIpilimumabPembrolizumabOptune / Optune Pax (TTFields)
Diagnosis and staging

CT and PET/CT; thoracoscopic biopsy with IHC panel (calretinin, WT1, D2-40; BAP1 and MTAP loss support malignancy); histology and BAP1/MTAP status recorded for treatment planning.

NCCN · MPM guideline
Histopathology & immunohistochemistryPET/CTCT (computed tomography)
First line, non-epithelioid

Nivolumab + ipilimumab (CheckMate 743) preferred; pembrolizumab + platinum-pemetrexed alternative.

NCCN · 1 (preferred)ESMO-MCBS · 4
NivolumabIpilimumabCheckMate 743PembrolizumabIND.227 / KEYNOTE-483Histology → first-line choice in mesothelioma
First line, epithelioid

Pembrolizumab + platinum-pemetrexed, nivolumab + ipilimumab, or platinum-pemetrexed ± bevacizumab, chosen by fitness and preference.

NCCN · 1 (chemo-IO and IO doublet); 2A (bevacizuma…ESMO-MCBS · 3
PembrolizumabIND.227 / KEYNOTE-483NivolumabIpilimumabPemetrexedMAPS
Maintenance

Continue immunotherapy per regimen; TTFields (Optune Lua) with pemetrexed-platinum under HDE approval; no maintenance chemotherapy standard.

NCCN · 2B (TTFields)
Optune / Optune Pax (TTFields)Tumour treating fields (TTFields)STELLAR
Second line

Nivolumab (CONFIRM: OS benefit vs placebo) or nivolumab-ipilimumab if not given first line; platinum-pemetrexed rechallenge or gemcitabine/vinorelbine if IO given first; trials.

NCCN · 2A
NivolumabPemetrexed
Surgery

Not recommended for cure outside trials after MARS 2; VATS pleurodesis or indwelling pleural catheter for effusion; extended P/D only in clinical trials.

NCCN · Selected centres/trials only
Extended pleurectomy/decortication & radical mesothelioma surgeryMARS 2
Radiotherapy

Palliative for chest wall pain; prophylactic tract irradiation not beneficial (SMART/PIT trials); hemithoracic IMRT after surgery only in trials.

IMRT / IGRT (modern external beam)
Peritoneal mesothelioma

Cytoreductive surgery with HIPEC in selected patients; systemic therapy extrapolated from pleural disease.

HIPEC / PIPAC (intraperitoneal chemotherapy)

Subtypes & biomarkers

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Subtypes
  • Epithelioid (~60-70%)
  • Biphasic (~20%)
  • Sarcomatoid (~10-20%, includes desmoplastic)
  • Peritoneal mesothelioma (~10-15% of all mesothelioma; treated with cytoreductive surgery and HIPEC)
  • Pericardial and testicular (rare)
Biomarkers clinicians test

Target prevalence in this cancer

Target / alterationPrevalenceSource
Mesothelin
Lower in sarcomatoid
85-100%
Wikipedia
PRMT5 (MTAP-deleted cancers)
40%

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 1960Wagner links mesothelioma to asbestos in South African miners
  2. 1989US EPA asbestos ban partly overturned (1991); many countries ban asbestos over the following decades
  3. 2003EMPHACIS: pemetrexed-cisplatin improves survival
    Pemetrexed
  4. 2004Pemetrexed-cisplatin approved
  5. 2004Pemetrexed approved: first mesothelioma drug
    Pemetrexed
  6. 2011MARS 1: extrapleural pneumonectomy shows harm; practice shifts to lung-sparing surgery
    Extended pleurectomy/decortication & radical mesothelioma surgery
  7. 2016MAPS: bevacizumab adds ~3 months
    MAPS
  8. 2019TTFields device approval (HDE) on STELLAR
    STELLAROptune / Optune Pax (TTFields)
  9. 2019LUME-Meso fails; nintedanib abandoned in mesothelioma
    LUME-MesoNintedanib
  10. 2020Nivolumab-ipilimumab first line
  11. 2020CheckMate 743: nivolumab-ipilimumab approved, first new first line in 16 years
    CheckMate 743NivolumabIpilimumab
  12. 2021CONFIRM: nivolumab improves survival in relapsed disease
    Nivolumab
  13. 2023IND.227/KEYNOTE-483 positive for pembrolizumab-chemotherapy
    IND.227 / KEYNOTE-483
  14. 2024MARS 2: surgery worsens survival; pembrolizumab-chemotherapy approved (September)
    MARS 2Pembrolizumab
  15. 2024BEAT-meso misses OS; non-epithelioid subgroup benefits
    BEAT-meso (ETOP 13-18)
  16. 2025CheckMate 743 five-year data: 14% vs 6% alive
    CheckMate 743
  17. 2026DREAM3R stopped early; PRMT5 inhibitors and mesothelin cell therapies advance
    DREAM3RPRMT5/MAT2A synthetic lethality for MTAP-deleted mesotheliomaRegionally delivered mesothelin CAR-T with PD-1 blockade

Pipeline

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Open problems

  • Sarcomatoid subtype.
  • No early detection despite known exposure.
  • Median survival still under two years with the best first-line regimens.
  • Epithelioid disease gains little from immunotherapy over chemotherapy; no predictive biomarker beyond histology.
  • No approved targeted therapy despite recurrent BAP1, CDKN2A/MTAP, and NF2 alterations.
  • Second-line options are weak once immunotherapy has been used first.
  • Surgery's role is now unclear for the small group of early, epithelioid, node-negative patients.
  • Response assessment is hard (modified RECIST for pleural rind); trials are small and slow.
  • Asbestos is still produced and used in several large countries; incidence will rise there for decades.
  • Peritoneal and rarer sites lack dedicated evidence.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Mesothelioma
condition: Mesothelioma
Open on ClinicalTrials.gov →

Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.

Landmark trials in OnCo

BEAT-meso (ETOP 13-18)CheckMate 743DREAM3RIND.227 / KEYNOTE-483LUME-MesoMAPSMARS 2STELLAR

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Mesothelioma

Generated from this cancer's standard of care, biomarkers, and pipeline · 27 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example Histology, BAP1, CDKN2A/MTAP deletion, Mesothelin, Histologydrives first-line choice), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Epithelioid, Biphasic, Sarcomatoid.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Unresectable

  1. For my situation (unresectable), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab-ipilimumab or chemo-IO; TTFields.
  2. Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Diagnosis and staging

  1. For my situation (diagnosis and staging), which of the standard options do you recommend and why?
    Why: Guideline options include: CT and PET/CT; thoracoscopic biopsy with IHC panel (calretinin, WT1, D2-40; BAP1 and MTAP loss support malignancy); histology and BAP1/MTAP status recorded for treatment planning.

First line, non-epithelioid

  1. For my situation (first line, non-epithelioid), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab + ipilimumab (CheckMate 743) preferred; pembrolizumab + platinum-pemetrexed alternative.
  2. Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CheckMate 743 and IND.227 / KEYNOTE-483 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

First line, epithelioid

  1. For my situation (first line, epithelioid), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab + platinum-pemetrexed, nivolumab + ipilimumab, or platinum-pemetrexed ± bevacizumab, chosen by fitness and preference.
  2. Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of IND.227 / KEYNOTE-483 and MAPS apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Maintenance

  1. For my situation (maintenance), which of the standard options do you recommend and why?
    Why: Guideline options include: Continue immunotherapy per regimen; TTFields (Optune Lua) with pemetrexed-platinum under HDE approval; no maintenance chemotherapy standard.
  2. Am I a candidate for Optune / Optune Pax (TTFields), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of STELLAR apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Second line

  1. For my situation (second line), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab (CONFIRM: OS benefit vs placebo) or nivolumab-ipilimumab if not given first line; platinum-pemetrexed rechallenge or gemcitabine/vinorelbine if IO given first; trials.
  2. Am I a candidate for Nivolumab, Pemetrexed, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Surgery

  1. For my situation (surgery), which of the standard options do you recommend and why?
    Why: Guideline options include: Not recommended for cure outside trials after MARS 2; VATS pleurodesis or indwelling pleural catheter for effusion; extended P/D only in clinical trials.
  2. How do the results of MARS 2 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Radiotherapy

  1. For my situation (radiotherapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Palliative for chest wall pain; prophylactic tract irradiation not beneficial (SMART/PIT trials); hemithoracic IMRT after surgery only in trials.

Peritoneal mesothelioma

  1. For my situation (peritoneal mesothelioma), which of the standard options do you recommend and why?
    Why: Guideline options include: Cytoreductive surgery with HIPEC in selected patients; systemic therapy extrapolated from pleural disease.

Any stage

  1. Are there clinical trials I could join, for example of Synthetic lethality approaches, PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma, Regionally delivered mesothelin CAR-T with PD-1 blockade, CAR-T cell therapy?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Sarcomatoid subtype”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “No early detection despite known exposure”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

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Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

19
Anti-angiogenic therapyAntibody-drug conjugate (ADC)Armoured, logic-gated & next-gen CARsCAR-T against stroma: fibroblasts and myeloid cellsCAR-T cell therapyCT (computed tomography)Cytotoxic chemotherapyExtended pleurectomy/decortication & radical mesothelioma surgeryFAPI PETHIPEC / PIPAC (intraperitoneal chemotherapy)Histopathology & immunohistochemistryImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Metabolic therapy: starving the tumour of a nutrientPET/CTSmall-molecule kinase inhibitorsSynthetic lethality approachesT-cell engagers (bispecific)Tumour treating fields (TTFields)

targets

8
CTLA-4FGFR2MesothelinPD-1PD-L1PRMT5 (MTAP-deleted cancers)VEGF / VEGFRVISTA

drugs

7
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
NegativeSmall-molecule kinase inhibitor (VEGFR/FGFR/PDGFR)
Nintedanib · Ofev (fibrosis); Vargatef (NSCLC, EU)
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedDevice (tumour treating fields)
Optune / Optune Pax (TTFields) · Optune
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedCytotoxic (antifolate)
Pemetrexed · Alimta (and generics)
Not mapped hereSemi-synthetic vinca alkaloid
Vinorelbine · Navelbine

companies

5
Boehringer IngelheimBristol Myers SquibbInsilico MedicineMerck & Co. (MSD)Novocure

institutions

9
ETOP IBCSG Partners FoundationIntergroupe Francophone de Cancérologie ThoraciqueInternational Association for the Study of Lung CancerMemorial Sloan Kettering Cancer CenterNCI Center for Cancer Research (intramural programme)Netherlands Cancer Institute (NKI-AvL)Shanghai Chest HospitalThe Christie NHS Foundation TrustThe Royal Marsden

pathways

4
Hippo–YAP/TAZp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activationVEGF angiogenesis

terms

8
Epithelioid vs sarcomatoid (biphasic) mesotheliomaImmune-related adverse events (irAEs)Malignant pleural effusion and ascitesPeritoneum and peritoneal metastasesPleuraPleurodesis and indwelling pleural catheterPneumonectomySynthetic lethality

trials

8
BEAT-meso (ETOP 13-18)CheckMate 743DREAM3RIND.227 / KEYNOTE-483LUME-MesoMAPSMARS 2STELLAR

pairings

1
Histology → first-line choice in mesothelioma

ideas

8
An open model bank for the rare tumours nobody has models forOne global rare cancer network with n-of-1 and Bayesian trial frameworksOne legal framework for pooling rare cancer data across bordersPartial lottery funding for good proposals in under-funded cancersPRMT5/MAT2A synthetic lethality for MTAP-deleted mesotheliomaRegionally delivered mesothelin CAR-T with PD-1 blockadeTreat the body cavity, not the bloodstream, for surface spreadTrial-in-a-box: a preconfigured protocol kit any hospital can open for a rare cancer

people

4
Julie R. BrahmerPatrick M. FordeRaffit HassanSolange Peters

bottlenecks

2
Rare and paediatric cancers without marketsSurgery and radiotherapy cure most, get least

Latest papers

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Literature trend571 papers in the last 12 months0% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Mesothelioma" OR ABSTRACT:"Mesothelioma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Mesothelioma, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

17
Anti-angiogenic therapyAntibody-drug conjugate (ADC)Armoured, logic-gated & next-gen CARsCAR-T against stroma: fibroblasts and myeloid cellsCAR-T cell therapyCT (computed tomography)Extended pleurectomy/decortication & radical mesothelioma surgeryFAPI PETHIPEC / PIPAC (intraperitoneal chemotherapy)Histopathology & immunohistochemistryImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Metabolic therapy: starving the tumour of a nutrientPET/CTSynthetic lethality approachesT-cell engagers (bispecific)Tumour treating fields (TTFields)

targets

7
CTLA-4MesothelinPD-1PD-L1PRMT5 (MTAP-deleted cancers)VEGF / VEGFRVISTA

drugs

7
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
NegativeSmall-molecule kinase inhibitor (VEGFR/FGFR/PDGFR)
Nintedanib · Ofev (fibrosis); Vargatef (NSCLC, EU)
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedDevice (tumour treating fields)
Optune / Optune Pax (TTFields) · Optune
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedCytotoxic (antifolate)
Pemetrexed · Alimta (and generics)
Not mapped hereSemi-synthetic vinca alkaloid
Vinorelbine · Navelbine

companies

5
Boehringer IngelheimBristol Myers SquibbInsilico MedicineMerck & Co. (MSD)Novocure

institutions

9
ETOP IBCSG Partners FoundationIntergroupe Francophone de Cancérologie ThoraciqueInternational Association for the Study of Lung CancerMemorial Sloan Kettering Cancer CenterNCI Center for Cancer Research (intramural programme)Netherlands Cancer Institute (NKI-AvL)Shanghai Chest HospitalThe Christie NHS Foundation TrustThe Royal Marsden

pathways

4
Hippo–YAP/TAZp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activationVEGF angiogenesis

terms

8
Epithelioid vs sarcomatoid (biphasic) mesotheliomaImmune-related adverse events (irAEs)Malignant pleural effusion and ascitesPeritoneum and peritoneal metastasesPleuraPleurodesis and indwelling pleural catheterPneumonectomySynthetic lethality

trials

8
BEAT-meso (ETOP 13-18)CheckMate 743DREAM3RIND.227 / KEYNOTE-483LUME-MesoMAPSMARS 2STELLAR

pairings

1
Histology → first-line choice in mesothelioma

ideas

8
An open model bank for the rare tumours nobody has models forOne global rare cancer network with n-of-1 and Bayesian trial frameworksOne legal framework for pooling rare cancer data across bordersPartial lottery funding for good proposals in under-funded cancersPRMT5/MAT2A synthetic lethality for MTAP-deleted mesotheliomaRegionally delivered mesothelin CAR-T with PD-1 blockadeTreat the body cavity, not the bloodstream, for surface spreadTrial-in-a-box: a preconfigured protocol kit any hospital can open for a rare cancer

people

4
Julie R. BrahmerPatrick M. FordeRaffit HassanSolange Peters

bottlenecks

2
Rare and paediatric cancers without marketsSurgery and radiotherapy cure most, get least