# Mesothelioma

Source: https://onco.cc/cancers/mesothelioma/  
OnCo record `mesothelioma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-07
- Tags: thoracic
- Group: thoracic
- Burden: Mesothelioma causes about 30,000 cases a year worldwide, ~3,000 in the US, almost all from asbestos exposure 20-50 years earlier, so incidence is still rising in Asia and parts of Europe. Immunotherapy has produced the first tail of long-term survivors; median survival is 12-18 months.
- 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: Histology (epithelioid vs sarcomatoid); BAP1; CDKN2A/MTAP deletion; Mesothelin; Histology (epithelioid vs non-epithelioid) drives first-line choice; BAP1 loss (diagnostic; germline BAP1 syndrome); CDKN2A/MTAP deletion (diagnostic; PRMT5-inhibitor target); Mesothelin (CAR-T, ADC, engager target); PD-L1 (weakly predictive); Soluble mesothelin-related peptides and fibulin-3 (research); Asbestos exposure history

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/mesothelioma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/mesothelioma/#overview [2 subtypes, 6 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/mesothelioma/#what-it-is [7 subtypes, 5 sites of spread]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/mesothelioma/#finding-it [11 biomarkers, 3 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/mesothelioma/#treating-it [9 settings, 2 regimens, 6 decisions with options]
- Evidence (own page): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/mesothelioma/evidence/ [26 trials, 17 milestones]
- The science (own page): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/mesothelioma/science/ [41 targets, 4 pathways, 6 preclinical models]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/mesothelioma/where-you-are/ [9 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/mesothelioma/#living-with-it [27 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/mesothelioma/coming/ [11 medicines, 26 trials, 9 ideas, 10 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/mesothelioma/data/ [165 connected records]

## Standard of care

- Unresectable: Nivolumab-ipilimumab or chemo-IO; TTFields. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Optune / Optune Pax (TTFields)](https://onco.cc/drugs/optune/))
- 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. ([Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [PET/CT](https://onco.cc/technologies/pet-ct/), [CT (computed tomography)](https://onco.cc/technologies/ct/))
- First line, non-epithelioid: Nivolumab + ipilimumab (CheckMate 743) preferred; pembrolizumab + platinum-pemetrexed alternative. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [CheckMate 743](https://onco.cc/trials/checkmate-743/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [IND.227 / KEYNOTE-483](https://onco.cc/trials/keynote-483/), [Histology → first-line choice in mesothelioma](https://onco.cc/pairings/histology-directs-first-line-meso/))
- First line, epithelioid: Pembrolizumab + platinum-pemetrexed, nivolumab + ipilimumab, or platinum-pemetrexed ± bevacizumab, chosen by fitness and preference. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [IND.227 / KEYNOTE-483](https://onco.cc/trials/keynote-483/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [MAPS](https://onco.cc/trials/maps/))
- Maintenance: Continue immunotherapy per regimen; TTFields (Optune Lua) with pemetrexed-platinum under HDE approval; no maintenance chemotherapy standard. ([Optune / Optune Pax (TTFields)](https://onco.cc/drugs/optune/), [Tumour treating fields (TTFields)](https://onco.cc/technologies/ttfields/), [STELLAR](https://onco.cc/trials/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. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/))
- Surgery: Not recommended for cure outside trials after MARS 2; VATS pleurodesis or indwelling pleural catheter for effusion; extended pleurectomy/decortication (P/D) only in clinical trials. ([Extended pleurectomy/decortication & radical mesothelioma surgery](https://onco.cc/technologies/pleurectomy-decortication/), [MARS 2](https://onco.cc/trials/mars-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)](https://onco.cc/technologies/imrt-igrt/))
- Peritoneal mesothelioma: Cytoreductive surgery with HIPEC in selected patients; systemic therapy extrapolated from pleural disease. ([HIPEC / PIPAC (intraperitoneal chemotherapy)](https://onco.cc/technologies/hipec/))

## State of the art

- 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.
- Five-year survival with nivolumab-ipilimumab 14% vs 6% with chemotherapy: a small but real tail of long-term survivors.
- MTAP deletion and BAP1 loss are routine diagnostic markers and emerging therapeutic handles.
- Mesothelin CAR-T delivered regionally has produced long survivors in phase 1.

## Open problems

- Sarcomatoid subtype.
- No early detection despite known exposure.
- Even the best first-line regimens give a median survival under two years; the tail of long survivors on immunotherapy is what to build on.
- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Mesothelioma
- NCI PDQ: malignant mesothelioma treatment: https://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq

## Connected records

- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Armoured, logic-gated & next-gen CARs](https://onco.cc/technologies/armored-car/), [CAR-T against stroma: fibroblasts and myeloid cells](https://onco.cc/technologies/stroma-directed-car/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [CT (computed tomography)](https://onco.cc/technologies/ct/), [Extended pleurectomy/decortication & radical mesothelioma surgery](https://onco.cc/technologies/pleurectomy-decortication/), [FAPI PET](https://onco.cc/technologies/fapi-pet/), [HIPEC / PIPAC (intraperitoneal chemotherapy)](https://onco.cc/technologies/hipec/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Metabolic therapy: starving the tumour of a nutrient](https://onco.cc/technologies/metabolic-therapy/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/), [Tumour treating fields (TTFields)](https://onco.cc/technologies/ttfields/)
- targets: [ARHGAP5](https://onco.cc/targets/arhgap5/), [BAP1](https://onco.cc/targets/bap1/), [CTLA-4](https://onco.cc/targets/ctla4/), [CYP2C8](https://onco.cc/targets/cyp2c8/), [DDX3X](https://onco.cc/targets/ddx3x/), [DGCR8](https://onco.cc/targets/dgcr8/), [ERCC1](https://onco.cc/targets/ercc1/), [FAT4](https://onco.cc/targets/fat4/), [FLG](https://onco.cc/targets/flg/), [GART (trifunctional purine synthesis enzyme)](https://onco.cc/targets/gart/), [HLA-DQA1](https://onco.cc/targets/hla-dqa1/), [LATS2](https://onco.cc/targets/lats2/), [Mesothelin](https://onco.cc/targets/mesothelin/), [MGA](https://onco.cc/targets/mga/), [NCOR1](https://onco.cc/targets/ncor1/), [NCOR2](https://onco.cc/targets/ncor2/), [NF2](https://onco.cc/targets/nf2/), [NFKB2](https://onco.cc/targets/nfkb2/), [NIN](https://onco.cc/targets/nin/), [PBRM1](https://onco.cc/targets/pbrm1/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [PDZD2](https://onco.cc/targets/pdzd2/), [PI4KA](https://onco.cc/targets/pi4ka/), [PRMT5 (MTAP-deleted cancers)](https://onco.cc/targets/prmt5-mtap/), [PTPRB](https://onco.cc/targets/ptprb/), [RHOA](https://onco.cc/targets/rhoa/), [SETD2](https://onco.cc/targets/setd2/), [SETDB1](https://onco.cc/targets/setdb1/), [SHTN1](https://onco.cc/targets/shtn1/), [SRGAP3](https://onco.cc/targets/srgap3/), [TAF15](https://onco.cc/targets/taf15/), [TBL1XR1](https://onco.cc/targets/tbl1xr1/), [TRAF7](https://onco.cc/targets/traf7/), [VEGF / VEGFR](https://onco.cc/targets/vegf/), [VISTA](https://onco.cc/targets/vista/), [WNK2](https://onco.cc/targets/wnk2/), [WT1](https://onco.cc/targets/wt1/)
- drugs: [Anetumab ravtansine](https://onco.cc/drugs/anetumab-ravtansine/), [EB-MF-CAR-NK-01](https://onco.cc/drugs/eb-mf-car-nk-01/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nintedanib](https://onco.cc/drugs/nintedanib/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Optune / Optune Pax (TTFields)](https://onco.cc/drugs/optune/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Raltitrexed](https://onco.cc/drugs/raltitrexed/), [Talc (intrapleural)](https://onco.cc/drugs/talc-sclerosant/), [Vinorelbine](https://onco.cc/drugs/vinorelbine/)
- companies: [A2 Biotherapeutics](https://onco.cc/companies/a2-biotherapeutics/), [Amphista Therapeutics](https://onco.cc/companies/amphista-therapeutics/), [Boehringer Ingelheim](https://onco.cc/companies/boehringer-ingelheim/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Eris Biotech](https://onco.cc/companies/eris-biotech/), [ETOP IBCSG Partners Foundation](https://onco.cc/companies/etop-ibcsg/), [Insilico Medicine](https://onco.cc/companies/insilico-medicine/), [Intergroupe Francophone de Cancérologie Thoracique](https://onco.cc/companies/ifct/), [Kissei Pharmaceutical](https://onco.cc/companies/kissei/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Novocure](https://onco.cc/companies/novocure/), [Orion, Orion Pharma](https://onco.cc/companies/orion-orion-pharma/), [Polaris Group](https://onco.cc/companies/polaris-group/)
- institutions: [International Association for the Study of Lung Cancer](https://onco.cc/institutions/iaslc/), [Leicester Cancer Research Centre / University Hospitals of Leicester](https://onco.cc/institutions/leicester-cancer-research-centre/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/), [NCI Center for Cancer Research (intramural programme)](https://onco.cc/institutions/nci-ccr/), [Netherlands Cancer Institute (NKI-AvL)](https://onco.cc/institutions/nki/), [Shanghai Chest Hospital](https://onco.cc/institutions/shanghai-chest-hospital/), [The Christie NHS Foundation Trust](https://onco.cc/institutions/the-christie/), [The Royal Marsden](https://onco.cc/institutions/royal-marsden/), [University of Western Australia](https://onco.cc/institutions/university-of-western-australia/)
- pathways: [Hippo-YAP/TAZ](https://onco.cc/pathways/hippo-yap/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Epithelioid vs sarcomatoid (biphasic) mesothelioma](https://onco.cc/terms/epithelioid-vs-sarcomatoid/), [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Malignant pleural effusion and ascites](https://onco.cc/terms/pleural-effusion/), [Peritoneum and peritoneal metastases](https://onco.cc/terms/peritoneum/), [Pleura](https://onco.cc/terms/pleura/), [Pleurodesis and indwelling pleural catheter](https://onco.cc/terms/pleurodesis/), [Pneumonectomy](https://onco.cc/terms/pneumonectomy/), [Synthetic lethality](https://onco.cc/terms/synthetic-lethality/)
- trials: [A 2-part Phase 1/2 Open-label Trial on ODM-212](https://onco.cc/trials/nct07563738/), [A Study of Oral 7HP349 (Alintegimod) in Combination With Ipilimumab Followed by Nivolumab Monotherapy](https://onco.cc/trials/nct06362369/), [A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas](https://onco.cc/trials/nct04104776/), [A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression](https://onco.cc/trials/nct06051695/), [Anetumab ravtansine versus vinorelbine in relapsed mesothelin-positive pleural mesothelioma](https://onco.cc/trials/anetumab-vs-vinorelbine-mpm/), [BEAT-meso (ETOP 13-18)](https://onco.cc/trials/beat-meso/), [CheckMate 743](https://onco.cc/trials/checkmate-743/), [DREAM3R](https://onco.cc/trials/dream3r/), [Dual-Target MSLN/FAP CAR-NK Cells for Pleural and Peritoneal Mesothelioma](https://onco.cc/trials/nct07510815/), [Hemithoracic irradiation with proton therapy in malignant pleural mesothelioma (UCL)](https://onco.cc/trials/ucl-proton-hemithoracic-mpm/), [IND.227 / KEYNOTE-483](https://onco.cc/trials/keynote-483/), [LUME-Meso](https://onco.cc/trials/lume-meso/), [MAPS](https://onco.cc/trials/maps/), [MARS 2](https://onco.cc/trials/mars-2/), [MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma](https://onco.cc/trials/nct06097728/), [Mithramycin for Lung, Esophagus, and Other Chest Cancers](https://onco.cc/trials/nct01624090/), [Pembrolizumab with or without anetumab ravtansine in mesothelin-positive pleural mesothelioma (NCI)](https://onco.cc/trials/nci-anetumab-pembrolizumab-mpm/), [Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer](https://onco.cc/trials/nct03907852/), [Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma](https://onco.cc/trials/nct01843374/), [STELLAR](https://onco.cc/trials/stellar/), [Study of ISM6331 in Participants With Advanced/Metastatic Mesothelioma or Other Advanced Solid Tumors](https://onco.cc/trials/nct06566079/), [Study of Volrustomig as Monotherapy or in Combination With Anti- Cancer Agents in Participants With Advanced/Metastatic Solid Tumors](https://onco.cc/trials/nct06535607/), [Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors](https://onco.cc/trials/nct04665206/), [TT-4 and TT-10 as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors and Pleural Mesothelioma](https://onco.cc/trials/nct04969315/), [Video-Assisted Surgery or Talc Pleurodesis in Treating Patients With Malignant Mesothelioma](https://onco.cc/trials/nct00821860/), [VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma](https://onco.cc/trials/nct03556228/)
- ideas: [An open model bank for the rare tumours nobody has models for](https://onco.cc/ideas/idea-bio2-rare-tumour-model-bank/), [Antibody-drug conjugates for mesothelioma: why they have failed so far and how they could work](https://onco.cc/ideas/idea-adc-for-mesothelioma/), [One global rare cancer network with n-of-1 and Bayesian trial frameworks](https://onco.cc/ideas/idea-moon-rare-cancer-global-network/), [One legal framework for pooling rare cancer data across borders](https://onco.cc/ideas/idea-data-cross-border-rare-cancer-pool/), [Partial lottery funding for good proposals in under-funded cancers](https://onco.cc/ideas/idea-fund-neglected-cancer-lottery/), [PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma](https://onco.cc/ideas/idea-mtap-prmt5-mesothelioma/), [Regionally delivered mesothelin CAR-T with PD-1 blockade](https://onco.cc/ideas/idea-mesothelin-car-t-regional/), [Treat the body cavity, not the bloodstream, for surface spread](https://onco.cc/ideas/idea-bio2-intracavitary-immunotherapy/), [Trial-in-a-box: a preconfigured protocol kit any hospital can open for a rare cancer](https://onco.cc/ideas/idea-tr1-rare-cancer-trial-in-a-box/)
- pairings: [Histology → first-line choice in mesothelioma](https://onco.cc/pairings/histology-directs-first-line-meso/)
- people: [Alfredo Addeo](https://onco.cc/people/alfredo-addeo/), [Anna K. Nowak](https://onco.cc/people/anna-nowak/), [Dean A. Fennell](https://onco.cc/people/dean-fennell/), [Hedy L. Kindler](https://onco.cc/people/hedy-kindler/), [Julie R. Brahmer](https://onco.cc/people/julie-brahmer/), [Karen Kelly](https://onco.cc/people/karen-kelly/), [Karim Vermaelen](https://onco.cc/people/karim-vermaelen/), [Michael Boyer](https://onco.cc/people/michael-boyer/), [Patrick M. Forde](https://onco.cc/people/patrick-forde/), [Paul Baas](https://onco.cc/people/paul-baas/), [Raffit Hassan](https://onco.cc/people/raffit-hassan/), [Rolf A. Stahel](https://onco.cc/people/rolf-stahel/), [Solange Peters](https://onco.cc/people/solange-peters/), [Valerie W. Rusch](https://onco.cc/people/valerie-rusch/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/)
- journals: [Lung cancer](https://onco.cc/journals/lung-cancer-journal/), [Thoracic cancer](https://onco.cc/journals/thoracic-cancer/)
- cancers: [Peritoneal mesothelioma](https://onco.cc/cancers/peritoneal-mesothelioma/), [Pleural mesothelioma](https://onco.cc/cancers/pleural-mesothelioma/)

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JSON: https://onco.cc/api/v1/entities/mesothelioma.json