New Markers for Management of Mesothelioma

 

 Buy Article Permissions and Reprints

Abstract

In this review, we provide an update on the status of cancer biomarkers for the clinical management of pleural mesothelioma, an aggressive cancer associated with asbestos exposure. Mesothelioma can be difficult to diagnose, and response to treatment is transient, even with recently adopted immune checkpoint inhibitor (ICI) combinations. Identification of mesothelioma-specific biomarkers could facilitate early diagnosis and tailor treatment strategies. Mesothelioma is characterized by frequent loss or alteration of the tumor suppressor genes cyclin-dependent kinase inhibitor 2A (CDKN2A) and BRCA1-associated protein-1 (BAP1). Accumulating data show these genes and/or their related protein products will be valuable tissue-based biomarkers for mesothelioma. Loss of BAP1, CDKN2A, p16, or methylthioadenosine phosphorylase provide pathologists with a reliable means of differentiating between mesothelioma and reactive mesothelial cell proliferations. This can aid diagnosis in difficult cases and is requisite for the identification of the new pathological entity malignant mesothelioma in situ. However, limited progress in identifying clinically useful soluble biomarkers in this cancer type has been made, with mesothelin remaining the benchmark. To date, results from studies to identify predictive biomarkers for ICI response have been disappointing. A recent retrospective study demonstrated BAP1 loss was predictive of improved survival following combination pemetrexed- and platinum-based chemotherapy. Validation of this result could have important clinical implications. Clinical trials aimed at targeting therapy based on biomarker expression are generally in the early phase setting, with overall results being moderate. The identification of biomarkers for mesothelioma remains a key research question due to their potential to improve patient outcomes in this deadly cancer.

Publication History

Article published online:
30 May 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

• References

• 1 Zhai Z, Ruan J, Zheng Y. et al. Assessment of global trends in the diagnosis of mesothelioma from 1990 to 2017. JAMA Netw Open 2021; 4 (08) e2120360
  CrossrefPubMedGoogle Scholar
• 2 Musk AW, Olsen N, Alfonso H. et al. Predicting survival in malignant mesothelioma. Eur Respir J 2011; 38 (06) 1420-1424
  CrossrefPubMedGoogle Scholar
• 3 Woodard GA, Jablons DM. Surgery for pleural mesothelioma, when it is indicated and why: arguments against surgery for malignant pleural mesothelioma. Transl Lung Cancer Res 2020; 9 (Suppl. 01) S86-S91
  CrossrefPubMedGoogle Scholar
• 4 Baas P, Scherpereel A, Nowak AK. et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet 2021; 397 (10272): 375-386
  CrossrefPubMedGoogle Scholar
• 5 Vogelzang NJ, Rusthoven JJ, Symanowski J. et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21 (14) 2636-2644
  CrossrefPubMedGoogle Scholar
• 6 Robinson BW, Creaney J, Lake R. et al. Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 2003; 362 (9396): 1612-1616
  CrossrefPubMedGoogle Scholar
• 7 Woolhouse I, Bishop L, Darlison L. et al. British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma. Thorax 2018; 73 (Suppl. 01) i1-i30
  CrossrefPubMedGoogle Scholar
• 8 Creaney J, Segal A, Olsen N. et al. Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma. Dis Markers 2014; 2014: 413946
  CrossrefPubMedGoogle Scholar
• 9 Popat S, Baas P, Faivre-Finn C. et al; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2022; 33 (02) 129-142
  CrossrefPubMedGoogle Scholar
• 10 Scherpereel A, Opitz I, Berghmans T. et al. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur Respir J 2020; 55 (06) 1900953
  CrossrefPubMedGoogle Scholar
• 11 Sheffield BS, Hwang HC, Lee AF. et al. BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations. Am J Surg Pathol 2015; 39 (07) 977-982
  CrossrefPubMedGoogle Scholar
• 12 Louw A, Badiei A, Creaney J, Chai MS, Lee YCG. Advances in pathological diagnosis of mesothelioma: what pulmonologists should know. Curr Opin Pulm Med 2019; 25 (04) 354-361
  CrossrefPubMedGoogle Scholar
• 13 Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res 2003; 9 (06) 2108-2113
  PubMedGoogle Scholar
• 14 WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Thoracic Tumours. 5th ed. Lyon, France:. International Agency for Research on Cancer; 2021
  Google Scholar
• 15 Klebe S, Nakatani Y, Dobra K. et al. The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis. Pathology 2021; 53 (04) 446-453
  CrossrefPubMedGoogle Scholar
• 16 Tsim S, Alexander L, Kelly C. et al. Serum proteomics and plasma fibulin-3 in differentiation of mesothelioma from asbestos-exposed controls and patients with other pleural diseases. J Thorac Oncol 2021; 16 (10) 1705-1717
  CrossrefPubMedGoogle Scholar
• 17 Pass HI, Levin SM, Harbut MR. et al. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med 2012; 367 (15) 1417-1427
  CrossrefPubMedGoogle Scholar
• 18 Ostroff RM, Mehan MR, Stewart A. et al. Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool. PLoS One 2012; 7 (10) e46091
  CrossrefPubMedGoogle Scholar
• 19 Creaney J, Dick IM, Meniawy TM. et al. Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax 2014; 69 (10) 895-902
  CrossrefPubMedGoogle Scholar
• 20 Schillebeeckx E, van Meerbeeck JP, Lamote K. Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis. Eur Respir Rev 2021; 30 (162) 210057
  CrossrefPubMedGoogle Scholar
• 21 US Food and Drug Administration. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). Accessed February 16, 2023 at: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
  PubMed
• 22 Kanayama M, Oyama R, Mori M. et al. Novel circulating tumor cell-detection chip combining conventional podoplanin and EGFR antibodies for all histological malignant pleural mesothelioma. Oncol Lett 2021; 22 (01) 522
  CrossrefPubMedGoogle Scholar
• 23 Pass HI, Giroux D, Kennedy C. et al; IASLC Staging Committee and Participating Institutions. Supplementary prognostic variables for pleural mesothelioma: a report from the IASLC staging committee. J Thorac Oncol 2014; 9 (06) 856-864
  CrossrefPubMedGoogle Scholar
• 24 Curran D, Sahmoud T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol 1998; 16 (01) 145-152
  CrossrefPubMedGoogle Scholar
• 25 Herndon II JE, Green MR, Chahinian AP, Corson JM, Suzuki Y, Vogelzang NJ. Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B. Chest 1998; 113 (03) 723-731
  CrossrefPubMedGoogle Scholar
• 26 Dacic S, Kothmaier H, Land S. et al. Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas. Virchows Arch 2008; 453 (06) 627-635
  CrossrefPubMedGoogle Scholar
• 27 Brcic L, Le Stang N, Gallob F. et al. A combination of MTAP and p16 immunohistochemistry can substitute for CDKN2A fluorescence in situ hybridization in diagnosis and prognosis of pleural mesotheliomas. Arch Pathol Lab Med 2023; 147 (03) 313-322
  CrossrefPubMedGoogle Scholar
• 28 McGregor SM, McElherne J, Minor A. et al. BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma. Hum Pathol 2017; 60: 86-94
  CrossrefPubMedGoogle Scholar
• 29 López-Ríos F, Chuai S, Flores R. et al. Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res 2006; 66 (06) 2970-2979
  CrossrefPubMedGoogle Scholar
• 30 Hmeljak J, Sanchez-Vega F, Hoadley KA. et al; TCGA Research Network. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov 2018; 8 (12) 1548-1565
  CrossrefPubMedGoogle Scholar
• 31 Farzin M, Toon CW, Clarkson A. et al. Loss of expression of BAP1 predicts longer survival in mesothelioma. Pathology 2015; 47 (04) 302-307
  CrossrefPubMedGoogle Scholar
• 32 Wang XY, Wang Z, Huang JB. et al. Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer. Tumour Biol 2017; 39 (06) 1010428317699111
  CrossrefPubMedGoogle Scholar
• 33 Louw A, Panou V, Szejniuk WM. et al. BAP1 loss by immunohistochemistry predicts improved survival to first-line platinum and pemetrexed chemotherapy for patients with pleural mesothelioma: a validation study. J Thorac Oncol 2022; 17 (07) 921-930
  CrossrefPubMedGoogle Scholar
• 34 Pulford E, Huilgol K, Moffat D, Henderson DW, Klebe S. Malignant mesothelioma, BAP1 immunohistochemistry, and VEGFA: does BAP1 have potential for early diagnosis and assessment of prognosis?. Dis Markers 2017; 2017: 1310478
  CrossrefPubMedGoogle Scholar
• 35 Cozzi I, Oprescu FA, Rullo E, Ascoli V. Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions. Diagn Cytopathol 2018; 46 (01) 9-14
  CrossrefPubMedGoogle Scholar
• 36 Forest F, Patoir A, Dal Col P. et al. Nuclear grading, BAP1, mesothelin and PD-L1 expression in malignant pleural mesothelioma: prognostic implications. Pathology 2018; 50 (06) 635-641
  CrossrefPubMedGoogle Scholar
• 37 Cantini L, Pecci F, Murrone A. et al. Questioning the prognostic role of BAP-1 immunohistochemistry in malignant pleural mesothelioma: a single center experience with systematic review and meta-analysis. Lung Cancer 2020; 146: 318-326
  CrossrefPubMedGoogle Scholar
• 38 Testa JR, Cheung M, Pei J. et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet 2011; 43 (10) 1022-1025
  CrossrefPubMedGoogle Scholar
• 39 Online Catalog of Human Genes and Genetic Disorders. Tumor predisposition syndrome 1 (TPDS1). Accessed August 4, 2022 at: https://www.omim.org/entry/614327
  PubMedGoogle Scholar
• 40 Rusch A, Ziltener G, Nackaerts K, Weder W, Stahel RA, Felley-Bosco E. Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases. Lung Cancer 2015; 87 (01) 77-79
  CrossrefPubMedGoogle Scholar
• 41 Baumann F, Flores E, Napolitano A. et al. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival. Carcinogenesis 2015; 36 (01) 76-81
  CrossrefPubMedGoogle Scholar
• 42 Pastorino S, Yoshikawa Y, Pass HI. et al. A subset of mesotheliomas with improved survival occurring in carriers of BAP1 and other germline mutations. J Clin Oncol 2018; 36 (35) JCO2018790352
  CrossrefPubMedGoogle Scholar
• 43 Hassan R, Morrow B, Thomas A. et al. Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Proc Natl Acad Sci U S A 2019; 116 (18) 9008-9013
  CrossrefPubMedGoogle Scholar
• 44 Chou A, Toon CW, Clarkson A, Sheen A, Sioson L, Gill AJ. The epithelioid BAP1-negative and p16-positive phenotype predicts prolonged survival in pleural mesothelioma. Histopathology 2018; 72 (03) 509-515
  CrossrefPubMedGoogle Scholar
• 45 Tian L, Zeng R, Wang X. et al. Prognostic significance of soluble mesothelin in malignant pleural mesothelioma: a meta-analysis. Oncotarget 2017; 8 (28) 46425-46435
  CrossrefPubMedGoogle Scholar
• 46 Hollevoet K, Nackaerts K, Thas O. et al. The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor. Chest 2012; 141 (02) 477-484
  CrossrefPubMedGoogle Scholar
• 47 Mori T, Tajima K, Hirama M. et al. The N-ERC index is a novel monitoring and prognostic marker for advanced malignant pleural mesothelioma. J Thorac Dis 2013; 5 (02) 145-148
  PubMedGoogle Scholar
• 48 Kirschner MB, Pulford E, Hoda MA. et al. Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis. Br J Cancer 2015; 113 (06) 963-969
  CrossrefPubMedGoogle Scholar
• 49 Pei D, Li Y, Liu X. et al. Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: evidence from a meta-analysis. Oncotarget 2017; 8 (08) 13030-13038
  CrossrefPubMedGoogle Scholar
• 50 Ghanim B, Rosenmayr A, Stockhammer P. et al. Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition. Sci Rep 2020; 10 (01) 5784
  CrossrefPubMedGoogle Scholar
• 51 Takamori S, Toyokawa G, Shimokawa M. et al. The C-reactive protein/albumin ratio is a novel significant prognostic factor in patients with malignant pleural mesothelioma: a retrospective multi-institutional study. Ann Surg Oncol 2018; 25 (06) 1555-1563
  CrossrefPubMedGoogle Scholar
• 52 Okita R, Okada M, Inokawa H, Murakami T, Ikeda E. Prognostic values of preoperative C-reactive protein, albumin, and neutrophil ratios in patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy. Surg Oncol 2022; 43: 101813
  CrossrefPubMedGoogle Scholar
• 53 Tabata C, Kanemura S, Tabata R. et al. Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma. J Clin Gastroenterol 2013; 47 (08) 684-688
  CrossrefPubMedGoogle Scholar
• 54 Hirayama N, Tabata C, Tabata R. et al. Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma. Respir Med 2011; 105 (01) 137-142
  CrossrefPubMedGoogle Scholar
• 55 Javadi J, Dobra K, Hjerpe A. Multiplex soluble biomarker analysis from pleural effusion. Biomolecules 2020; 10 (08) 1113
  CrossrefPubMedGoogle Scholar
• 56 Creaney J, Dick IM, Segal A, Musk AW, Robinson BWS. Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma. Lung Cancer 2013; 82 (03) 491-498
  CrossrefPubMedGoogle Scholar
• 57 De Fonseka D, Arnold DT, Morley AJ. et al. Lymphocyte predominance in blood, pleural fluid, and tumour stroma; a prognostic marker in pleural mesothelioma. BMC Pulm Med 2022; 22 (01) 173
  CrossrefPubMedGoogle Scholar
• 58 Cedrés S, Ponce-Aix S, Zugazagoitia J. et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One 2015; 10 (03) e0121071
  CrossrefPubMedGoogle Scholar
• 59 Brcic L, Klikovits T, Megyesfalvi Z. et al. Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study. Transl Lung Cancer Res 2021; 10 (04) 1594-1607
  CrossrefPubMedGoogle Scholar
• 60 Carbone M, Adusumilli PS, Alexander Jr HR. et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin 2019; 69 (05) 402-429
  CrossrefPubMedGoogle Scholar
• 61 Sato Y, Tomita M, Soga T, Ochiai A, Makinoshima H. Upregulation of thymidylate synthase induces pemetrexed resistance in malignant pleural mesothelioma. Front Pharmacol 2021; 12: 718675
  CrossrefPubMedGoogle Scholar
• 62 Zucali PA, Giovannetti E, Destro A. et al. Thymidylate synthase and excision repair cross-complementing group-1 as predictors of responsiveness in mesothelioma patients treated with pemetrexed/carboplatin. Clin Cancer Res 2011; 17 (08) 2581-2590
  CrossrefPubMedGoogle Scholar
• 63 Christoph DC, Asuncion BR, Mascaux C. et al. Folylpoly-glutamate synthetase expression is associated with tumor response and outcome from pemetrexed-based chemotherapy in malignant pleural mesothelioma. J Thorac Oncol 2012; 7 (09) 1440-1448
  CrossrefPubMedGoogle Scholar
• 64 Lustgarten DE, Deshpande C, Aggarwal C. et al. Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma. J Thorac Oncol 2013; 8 (04) 469-477
  CrossrefPubMedGoogle Scholar
• 65 Mairinger F, Vollbrecht C, Halbwedl I. et al. Reduced folate carrier and folylpolyglutamate synthetase, but not thymidylate synthase predict survival in pemetrexed-treated patients suffering from malignant pleural mesothelioma. J Thorac Oncol 2013; 8 (05) 644-653
  CrossrefPubMedGoogle Scholar
• 66 Scherpereel A, Mazieres J, Greillier L. et al; French Cooperative Thoracic Intergroup. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol 2019; 20 (02) 239-253
  CrossrefPubMedGoogle Scholar
• 67 Disselhorst MJ, Quispel-Janssen J, Lalezari F. et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med 2019; 7 (03) 260-270
  CrossrefPubMedGoogle Scholar
• 68 Pistillo MP, Fontana V, Morabito A. et al; Italian Melanoma Intergroup (IMI). Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study. Cancer Immunol Immunother 2019; 68 (01) 97-107
  CrossrefPubMedGoogle Scholar
• 69 Kern R, Panis C. CTLA-4 expression and its clinical significance in breast cancer. Arch Immunol Ther Exp (Warsz) 2021; 69 (01) 16
  CrossrefPubMedGoogle Scholar
• 70 Fennell DA, King A, Mohammed S. et al; MiST2 study group. Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial. Lancet Oncol 2022; 23 (03) 374-381
  CrossrefPubMedGoogle Scholar
• 71 Rathkey D, Khanal M, Murai J. et al. Sensitivity of mesothelioma cells to PARP inhibitors is not dependent on BAP1 but is enhanced by temozolomide in cells with high-schlafen 11 and low-O6-methylguanine-DNA methyltransferase expression. J Thorac Oncol 2020; 15 (05) 843-859
  CrossrefPubMedGoogle Scholar
• 72 Zauderer MG, Szlosarek PW, Le Moulec S. et al. EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. Lancet Oncol 2022; 23 (06) 758-767
  CrossrefPubMedGoogle Scholar
• 73 Fennell DA, King A, Mohammed S. et al; MiST1 study group. Rucaparib in patients with BAP1-deficient or BRCA1-deficient mesothelioma (MiST1): an open-label, single-arm, phase 2a clinical trial. Lancet Respir Med 2021; 9 (06) 593-600
  CrossrefPubMedGoogle Scholar
• 74 Shapiro IM, Kolev VN, Vidal CM. et al. Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship. Sci Transl Med 2014; 6 (237) 237ra68
  CrossrefPubMedGoogle Scholar
• 75 Mak G, Soria JC, Blagden SP. et al. A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours. Br J Cancer 2019; 120 (10) 975-981
  CrossrefPubMedGoogle Scholar
• 76 Fennell DA, Baas P, Taylor P. et al. Maintenance defactinib versus placebo after first-line chemotherapy in patients with merlin-stratified pleural mesothelioma: COMMAND-a double-blind, randomized, phase II study. J Clin Oncol 2019; 37 (10) 790-798
  CrossrefPubMedGoogle Scholar
• 77 Hassan R, Miller AC, Sharon E. et al. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci Transl Med 2013; 5 (208) 208ra147
  CrossrefPubMedGoogle Scholar
• 78 Hassan R, Sharon E, Thomas A. et al. Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125. Cancer 2014; 120 (21) 3311-3319
  CrossrefPubMedGoogle Scholar
• 79 Hassan R. Mesothelin-targeted immunotoxin LMB-100 in combination with SEL-110 in subjects with malignant pleural or peritoneal mesothelioma. ClinicalTrials.gove identifier: NCT03436732. Accessed November 22, 2019 at: https://clinicaltrials.gov/ct2/show/NCT03436732
  PubMedGoogle Scholar
• 80 Kindler HL, Novello S, Bearz A. et al. Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. Lancet Oncol 2022; 23 (04) 540-552
  CrossrefPubMedGoogle Scholar
• 81 Quispel-Janssen J, van der Noort V, de Vries JF. et al. Programmed death 1 blockade with nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol 2018; 13 (10) 1569-1576
  CrossrefPubMedGoogle Scholar
• 82 Hassan R, Thomas A, Nemunaitis JJ. et al. Efficacy and safety of avelumab treatment in patients with advanced unresectable mesothelioma: phase 1b results from the JAVELIN Solid Tumor Trial. JAMA Oncol 2019; 5 (03) 351-357
  CrossrefPubMedGoogle Scholar
• 83 Fujimoto N, Okada M, Kijima T. et al. Clinical efficacy and safety of nivolumab in Japanese patients with malignant pleural mesothelioma: 3-year results of the MERIT study. JTO Clin Res Rep 2020; 2 (03) 100135
  PubMedGoogle Scholar
• 84 Calabrò L, Morra A, Giannarelli D. et al. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med 2018; 6 (06) 451-460
  CrossrefPubMedGoogle Scholar
• 85 Nowak AK, Lesterhuis WJ, Kok PS. et al. Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in. Lancet Oncol 2020; 21 (09) 1213-1223
  CrossrefPubMedGoogle Scholar
• 86 Fennell DA, Ewings S, Ottensmeier C. et al; CONFIRM trial investigators. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol 2021; 22 (11) 1530-1540
  CrossrefPubMedGoogle Scholar
• 87 Popat S, Curioni-Fontecedro A, Dafni U. et al. 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. Ann Oncol 2020; 31 (12) 1734-1745
  CrossrefPubMedGoogle Scholar
• 88 Forde PM, Anagnostou V, Sun Z. et al. Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial. Nat Med 2021; 27 (11) 1910-1920
  CrossrefPubMedGoogle Scholar
• 89 Ghafoor A, Mian I, Wagner C. et al. Phase 2 study of olaparib in malignant mesothelioma and correlation of efficacy with germline or somatic mutations in BAP1 gene. JTO Clin Res Rep 2021; 2 (10) 100231
  PubMedGoogle Scholar
• 90 Rottey S, Clarke J, Aung K. et al. Phase I/IIa Trial of BMS-986148, an anti-mesothelin antibody-drug conjugate, alone or in combination with nivolumab in patients with advanced solid tumors. Clin Cancer Res 2022; 28 (01) 95-105
  CrossrefPubMedGoogle Scholar
• 91 Adusumilli PS, Zauderer MG, Rivière I. et al. A Phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab. Cancer Discov 2021; 11 (11) 2748-2763
  CrossrefPubMedGoogle Scholar
• 92 Hassan R, Alley E, Kindler H. et al. Clinical response of live-attenuated, Listeria monocytogenes expressing mesothelin (CRS-207) with chemotherapy in patients with malignant pleural mesothelioma. Clin Cancer Res 2019; 25 (19) 5787-5798
  CrossrefPubMedGoogle Scholar
• 93 Alley EW, Tanvetyanon T, Jahan TM. et al. A phase II single-arm study of CRS-207 with pembrolizumab (pembro) in previously treated malignant pleural mesothelioma (MPM). J Clin Oncol 2019; 37 (08) 29
  CrossrefPubMedGoogle Scholar