{"entity":{"id":"histology-directs-first-line-meso","kind":"pairing","name":"Histology → first-line choice in mesothelioma","aka":[],"tldr":"Read the tumour type under the microscope first: non-epithelioid tumours should get immunotherapy up front; epithelioid tumours can reasonably get either immunotherapy or chemo-immunotherapy.","summary":"In mesothelioma the histological subtype read by histopathology and immunohistochemistry now directs the first-line choice, making this a diagnostic-therapeutic pairing. Sarcomatoid and biphasic tumours are chemoresistant but more immune-infiltrated, whereas epithelioid tumours retain sensitivity to pemetrexed-based chemotherapy. In pre-specified subgroups of CheckMate 743, nivolumab plus ipilimumab gave a large survival advantage over chemotherapy in non-epithelioid disease but only a small one in epithelioid disease, and pembrolizumab plus chemotherapy in IND.227 / KEYNOTE-483 and BEAT-meso showed the same pattern. Guidelines therefore favour immunotherapy up front for non-epithelioid tumours, while epithelioid tumours can receive either immunotherapy or chemo-immunotherapy.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02899299: CheckMate 743","url":"https://clinicaltrials.gov/study/NCT02899299"},{"label":"ClinicalTrials.gov NCT02784171: IND.227 / KEYNOTE-483","url":"https://clinicaltrials.gov/study/NCT02784171"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab","ipilimumab","pembrolizumab","pemetrexed"],"companies":[],"institutions":[],"pathways":[],"terms":["epithelioid-vs-sarcomatoid"],"trials":["checkmate-743","keynote-483"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"histopathology-ihc","b":"checkpoint-inhibitor","rationale":"Sarcomatoid tumours are chemoresistant but more immune-infiltrated; epithelioid tumours retain chemosensitivity.","evidence":"Pre-specified subgroup analyses of two phase 3 trials plus BEAT-meso.","pairingType":"diagnostic-therapeutic"},"route":"/pairings/histology-directs-first-line-meso/","neighbours":{"cancer":[{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}],"term":[{"id":"epithelioid-vs-sarcomatoid","kind":"term","name":"Epithelioid vs sarcomatoid (biphasic) mesothelioma","route":"/terms/epithelioid-vs-sarcomatoid/"}],"trial":[{"id":"checkmate-743","kind":"trial","name":"CheckMate 743","route":"/trials/checkmate-743/"},{"id":"keynote-483","kind":"trial","name":"IND.227 / KEYNOTE-483","route":"/trials/keynote-483/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}}