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Optimal Therapy of Advanced Stage Mesothelioma

Opinion statement

The optimal treatment of patients with advanced malignant pleural mesothelioma (MPM) has not yet been discovered. With the aid of an increased insight in the molecular pathways and the development of combinations of Immuno-Oncology (IO), drugs new therapies are available. The personalization of treatment by cell cultures and pathway analysis attracts more attention nowadays. It is conceivable that in the near future the treatment of patients with MPM will consist of a combination of IO drugs or specific pathway inhibitors.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Asbestos, asbestosis, and cancer: the Helsinki criteria for diagnosis and attribution. Scand J Work Environ Health. 1997;23(4):311–6.

  2. Stayner L, Welch LS, Lemen R. The worldwide pandemic of asbestos-related diseases. Annu rev Public Health. 2013;34:205–16. doi:10.1146/annurev-publhealth-031811-124704.

    Article  PubMed  Google Scholar 

  3. Francisci S, Minicozzi P, Pierannunzio D, Ardanaz E, Eberle A, Grimsrud TK, et al. Survival patterns in lung and pleural cancer in Europe 1999-2007: results from the EUROCARE-5 study. European journal of cancer (Oxford, England : 1990). 2015; doi:10.1016/j.ejca.2015.07.033.

  4. Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, et al. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet (London, England). 2008;371(9625):1685–94. doi:10.1016/s0140-6736(08)60727-8.

    CAS  Article  Google Scholar 

  5. •• Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet (London, England). 2016;387(10026):1405–14. doi:10.1016/s0140-6736(15)01238-6. Promising data of additional effect of bevacizumab to the standard of care in patients with malignant pleural mesothelioma.

    CAS  Article  Google Scholar 

  6. Baas P, Fennell D, Kerr KM, Van Schil PE, Haas RL, Peters S. Malignant pleural mesothelioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology. 2015;26(Suppl 5):v31–9. doi:10.1093/annonc/mdv199.

    Article  Google Scholar 

  7. Stahel RA, Riesterer O, Xyrafas A, Opitz I, Beyeler M, Ochsenbein A, et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. The Lancet oncology. 2015;16(16):1651–8. doi:10.1016/s1470-2045(15)00208-9.

    Article  PubMed  Google Scholar 

  8. de Graaf-Strukowska L, van der Zee J, van Putten W, Senan S. Factors influencing the outcome of radiotherapy in malignant mesothelioma of the pleura—a single-institution experience with 189 patients. Int J Radiat Oncol Biol Phys. 1999;43(3):511–6.

    Article  PubMed  Google Scholar 

  9. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003;21(14):2636–44. doi:10.1200/jco.2003.11.136.

    CAS  Article  Google Scholar 

  10. van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer lung cancer group and the National Cancer Institute of Canada. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(28):6881–9. doi:10.1200/jco.20005.14.589.

    Article  Google Scholar 

  11. Kindler HL, Karrison TG, Gandara DR, Lu C, Krug LM, Stevenson JP, et al. Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30(20):2509–15. doi:10.1200/jco.2011.41.5869.

    CAS  Article  Google Scholar 

  12. • Scagliotti GV, Gaafar R, Nowak A, Vogelzang NJ, Von Wangenheim U, Morsli N, et al. P2.01: LUME-MeSO: phase II/III study of nintedanib + pemetrexed/cisplatin in patients with malignant pleural mesothelioma: track: SCLC, mesothelioma, thymoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2016;11(10s):S216. doi:10.1016/j.jtho.2016.08.075. Promising preliminary data on the additional effect of nintedanib for pleural malignant mesothelioma.

    Article  Google Scholar 

  13. F G. Nintedanib plus pemetrexed/cisplatin in patients with MPM: Phase II findings from the placebo-controlled LUME-Meso trial. Abstract OA22.02. World Conference on Lung Cancer; Vienna2016.

  14. van den Bogaert DP, Pouw EM, van Wijhe G, Vernhout RM, Surmont VF, Hoogsteden HC, et al. Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2006;1(1):25–30.

    Article  Google Scholar 

  15. Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, et al. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. The Lancet Oncology. 2013;14(6):543–51. doi:10.1016/s1470-2045(13)70125-6.

    CAS  Article  PubMed  Google Scholar 

  16. Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, et al. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. The Lancet Oncology. 2015;16(4):447–56. doi:10.1016/s1470-2045(15)70056-2.

    CAS  Article  PubMed  Google Scholar 

  17. Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 2012;483(7391):570–5. doi:10.1038/nature11005.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Baas P. PeRsOnalized treatment fOr patients with pleural eFfusions due to malignant pleural mesothelioma or lung cancer in second or third line. An open label phase II study (PROOF). 2014. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4775.

  19. • Szlosarek PW, Steele JP, Nolan L, Gilligan D, Taylor P, Spicer J, et al. Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma: a randomized clinical trial. JAMA Oncology. 2017;3(1):58–66. doi:10.1001/jamaoncol.2016.3049. Phase II study investigating ADI-PEG for patients with ASS-1 deficient malignant pleural mesothelioma.

    Article  PubMed  Google Scholar 

  20. Wangpaichitr M, Wu C, Bigford G, Theodoropoulos G, You M, Li YY, et al. Combination of arginine deprivation with TRAIL treatment as a targeted-therapy for mesothelioma. Anticancer res. 2014;34(12):6991–9.

    CAS  PubMed  Google Scholar 

  21. Pardoll D. The blockade of immune checkpoints in cancer immunotherapy. Nat rev Cancer. 2012;12:252–64.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Cedrés SP-AS, Zugazagoitia J, et al. Analysis of expressione of programmed cell death one ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015;10(3):e0121071.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mandfield AS, Roden AC, Peikert T, Sheinin YM, Harrington SM, Krco CJ, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9(7):1036–40.

    Article  Google Scholar 

  24. Kindler HL. Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): results from the global, double-blind, placebo-controlled DETERMINE study. J Clin Oncol. 2016; 34(suppl; abstr 8502). ASCO Annual Meeting 2016.

  25. Baas P. A phase II study of malignant pleural mesothlioma (NivoMes): with translational research (TR) biopsies. Abstract OA13.01. World Conference on Lung Cancer; Vienna2016.

  26. Kindler HL. Phase II trial of pembrolizumab in patients with malignant mesothelioma (MM): interim analysis. Abstract OA 13.02 World Conference on Lung Cancer; Vienna2016.

  27. Alley. Long-term overall survival for patients with malignant pleural mesothelioma on pembrolizumab enrolled in KEYNOTE-28. Abstract OA 13.03. World Conference on Lung Cancer; Vienna2016.

  28. Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. The Lancet Oncology. 2017; doi:10.1016/s1470-2045(17)30169-9.

  29. Curran MAMW, Yagita H, Allison PJ. PD-1 and CTLA4 combination blockade expands infiltrating T cells and reducesregulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S a. 2010;107:4275–80.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Pastan I, Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer res. 2014;74(11):2907–12. doi:10.1158/0008-5472.can-14-0337.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. •• Hassan R, Kindler HL, Jahan T, Bazhenova L, Reck M, Thomas A, et al. Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2014;20(23):5927–36. doi:10.1158/1078-0432.ccr-14-0804. Evaluation of antibody-based therapeutic agents directed at mesothelin.

    CAS  Article  Google Scholar 

  32. Hassan R, Thomas A, Alewine C, Le DT, Jaffee EM, Pastan I. Mesothelin immunotherapy for cancer: ready for prime time? Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016;34(34):4171–9.

    Article  Google Scholar 

  33. Ventii KH, Devi NS, Friedrich KL, Chernova TA, Tighiouart M, Van Meir EG, et al. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer res. 2008;68(17):6953–62. doi:10.1158/0008-5472.can-08-0365.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43(7):668–72. doi:10.1038/ng.855.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Paul Baas MD.

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Conflict of Interest

Maria M.J. Disselhorst declares that she has no conflict of interest.

Sjaak J.A. Burgers has served as a consultant for Roche, Boehringer and AstraZeneca. He has not received any personal reimbursements.

Paul Baas has received research grants from or has served as a consultant for Merck, Bristol-Meyers Squibb, Polaris and Pfizer. He has not received any personal reimbursements.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Lung Cancer

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Disselhorst, M.M.J., Burgers, S.J.A. & Baas, P. Optimal Therapy of Advanced Stage Mesothelioma. Curr. Treat. Options in Oncol. 18, 48 (2017). https://doi.org/10.1007/s11864-017-0488-7

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  • DOI: https://doi.org/10.1007/s11864-017-0488-7

Keywords

  • Malignant pleural mesothelioma
  • Therapy
  • Immuno-oncology drugs
  • Pathway inhibitors