{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T21:39:44Z","timestamp":1784151584168,"version":"3.55.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: This study aimed to evaluate the effectiveness of immunotherapy compared to chemotherapy across different treatment lines in patients with pleural mesothelioma. It also sought to identify factors influencing the success of immunotherapy, such as histological subtype, PD-L1 expression, type of asbestos exposure, and metastatic status. Materials and Methods: A retrospective analysis was conducted with 60 patients diagnosed with pleural mesothelioma. Data on age, gender, histological subtype, and asbestos exposure were collected for all patients and PD-L1 expression was assessed in a subset of patients. Patients received either chemotherapy or immunotherapy as first-, second-, and third-line treatments, and progression-free survival (PFS) and treatment responses were evaluated. Results: Among the 60 patients, 35 (58.3%) were male and the median age was 59 years. The majority (71.7%) had epithelioid histology and 28.3% had distant metastases. Asbestos exposure was documented in 65% of the cases. PD-L1 expression of \u22651% was found in 13 of 17 patients tested. First-line treatments included immunotherapy for 11 patients and chemotherapy for the others, with immunotherapy achieving median PFS of 9 months versus 6 months for chemotherapy, although the difference was not statistically significant. In third-line treatments, immunotherapy significantly outperformed chemotherapy with median PFS of 6 months compared to 3 months (p = 0.048). Absence of metastasis and prior asbestos exposure in an endemic region were linked to better immunotherapy outcomes. Conclusion: Immunotherapy shows increased efficacy in later treatment lines for pleural mesothelioma, especially for patients without metastases or with prior endemic asbestos exposure. Tailored therapeutic strategies should be further explored in prospective studies.<\/jats:p>","DOI":"10.3390\/medicina61040638","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:21:04Z","timestamp":1743398464000},"page":"638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of Immunotherapy Versus Chemotherapy in Advanced Pleural Mesothelioma: A Turkish Oncology Group (TOG) Study"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-8180","authenticated-orcid":false,"given":"Ziya","family":"Kalkan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Mardin Training and Research Hospital, Mardin 47100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senar","family":"Ebinc","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Van Yuzuncu Yil University Faculty of Medicine, Van 65100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4058-6929","authenticated-orcid":false,"given":"Murat","family":"Arcagok","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dicle University Faculty of Medicine, Diyarbakir 21100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-6966","authenticated-orcid":false,"given":"Ahmet","family":"Bilici","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozcan","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul 34000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadettin","family":"Kilickap","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istinye University Faculty of Medicine, Istanbul 34000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6924-9467","authenticated-orcid":false,"given":"Deniz Can","family":"Guven","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara 06000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Murat","family":"Tatli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya 07000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet Taner","family":"Sumbul","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Baskent University Adana Dr. Turgut Noyan Application and Research Center, Adana 01100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-0756","authenticated-orcid":false,"given":"Nil Molinas","family":"Mandel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, American Hospital, Istanbul 34000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akin","family":"Ozturk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital, Istanbul 34000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7854-097X","authenticated-orcid":false,"given":"Murat","family":"Bardakci","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gazi Yasargil Training and Research Hospital, Diyarbakir 21100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2111-7131","authenticated-orcid":false,"given":"Serdar","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Ataturk Sanatoryum Training and Research Hospital, Ankara 06000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet Ali","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dicle University Faculty of Medicine, Diyarbakir 21100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.15585\/mmwr.mm6608a3","article-title":"Malignant mesothelioma mortality\u2014United States, 1999\u20132015","volume":"66","author":"Mazurek","year":"2017","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1183\/09031936.00000811","article-title":"Predicting survival in malignant mesothelioma","volume":"38","author":"Musk","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1136\/oem.17.4.260","article-title":"Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province","volume":"17","author":"Wagner","year":"1960","journal-title":"Occup. Environ. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1136\/oem.54.6.403","article-title":"Routes of asbestos exposure and the development of mesothelioma in an English region","volume":"54","author":"Howel","year":"1997","journal-title":"Occup. Environ. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/carcin\/bgz004","article-title":"Prognostic factors of survival in patients with malignant pleural mesothelioma: An analysis of the National Cancer Database","volume":"40","author":"Alpert","year":"2019","journal-title":"Carcinogenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","article-title":"Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma","volume":"21","author":"Vogelzang","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(15)01238-6","article-title":"Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): A randomised, controlled, open-label, phase 3 trial","volume":"387","author":"Zalcman","year":"2016","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): A multicentre, randomised, open-label, phase 3 trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Campbell, N.P., and Kindler, H.L. (2011). Update on malignant pleural mesothelioma. Seminars in Respiratory and Critical Care Medicine, Thieme Medical Publishers.","DOI":"10.1055\/s-0031-1272874"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1200\/JCO.2000.18.23.3912","article-title":"Phase II study of vinorelbine in patients with malignant pleural mesothelioma","volume":"18","author":"Steele","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/S1470-2045(21)00404-6","article-title":"Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): A randomised, double-blind, placebo-controlled, phase 2 trial","volume":"22","author":"Pinto","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1200\/JCO.21.02229","article-title":"Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma","volume":"40","author":"Wolchok","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/S1470-2045(22)00559-9","article-title":"Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): Distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial","volume":"23","author":"Long","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tykodi, S.S., Gordan, L.N., Alter, R.S., Arrowsmith, E., Harrison, M.R., Singal, R., Van Veldhuizen, P., George, D.J., Hutson, T., and Zhang, J. (2022). Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: Results from the phase 3b\/4 CheckMate 920 trial. J. Immunother. Cancer, 10.","DOI":"10.1136\/jitc-2021-003844"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S1470-2045(20)30436-8","article-title":"Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomised, open-label, phase 3 trial","volume":"21","author":"Powles","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1\u2013positive non\u2013small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMoa1917346","article-title":"Atezolizumab for first-line treatment of PD-L1\u2013selected patients with NSCLC","volume":"383","author":"Herbst","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0140-6736(21)00228-2","article-title":"Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: A multicentre, open-label, global, phase 3, randomised, controlled trial","volume":"397","author":"Sezer","year":"2021","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S1470-2045(17)30446-1","article-title":"Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): A multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial","volume":"18","author":"Maio","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1016\/j.annonc.2020.09.009","article-title":"A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: The European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial","volume":"31","author":"Popat","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/S1470-2045(21)00471-X","article-title":"Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): A multicentre, double-blind, randomised, phase 3 trial","volume":"22","author":"Fennell","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1038\/s41591-022-01977-y","article-title":"Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: A randomized, controlled, double-blind phase 3 trial","volume":"28","author":"Gogishvili","year":"2022","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1053\/rmed.2001.1108","article-title":"p53, p21 and metallothionein immunoreactivities in patients with malignant pleural mesothelioma: Correlations with the epidemiological features and prognosis of mesotheliomas with environmental asbestos exposure","volume":"95","author":"Isik","year":"2001","journal-title":"Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1159\/000056289","article-title":"Incidence of malignant pleural mesothelioma due to environmental asbestos fiber exposure in the southeast of Turkey","volume":"67","author":"Asan","year":"2000","journal-title":"Respiration"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1378\/chest.102.3.790","article-title":"Malignant pleural mesothelioma due to environmental mineral fiber exposure in Turkey: Analysis of 135 cases","volume":"102","author":"Emri","year":"1992","journal-title":"Chest"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0954-6111(99)90318-9","article-title":"Environmental asbestos exposure and malignant pleural mesothelioma","volume":"93","author":"Metintas","year":"1999","journal-title":"Respir. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.21037\/tlcr-20-673","article-title":"Immunotherapy in malignant pleural mesothelioma: A review of literature data","volume":"10","author":"Menis","year":"2021","journal-title":"Transl. Lung Cancer Res."}],"updated-by":[{"DOI":"10.3390\/medicina61111997","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000}}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/4\/638\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T10:56:55Z","timestamp":1762513015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/4\/638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["medicina61040638"],"URL":"https:\/\/doi.org\/10.3390\/medicina61040638","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]}}}