Current Chemotherapy Strategies in Malignant Pleural Mesothelioma

Cornedine Jannette de Gooijer; Paul Baas; Jacobus Adrianus Burgers

Disclosures

Transl Lung Cancer Res. 2018;7(5) 

In This Article

Abstract and Introduction

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a 5-year survival rate of ~10%. Since most patients present with irresectable disease, the vast majority is treated with chemotherapy. The only registered therapy for MPM is platinum-pemetrexed doublet therapy, although only up to half of patients have clinical benefit from this palliative treatment. Of the anti-angiogenesis agents, only bevacizumab and nintedanib have shown activity with platinum-pemetrexed doublet therapy. Other anti-angiogenesis agents like thalidomide did not prolong (progression free) survival or response rate. Eventually, all patients will get a recurrence and no active second line therapy has been identified to date. The clinical benefit of (switch) maintenance therapy after first line treatment and combination strategies of different chemotherapies with angiogenesis inhibitors are currently under investigation. The major challenges are finding optimal treatment combinations and to select the adequate treatment for an individual patient. This review focusses on the current standard of chemotherapy and new systemic therapy strategies under investigation.

Introduction

Chemotherapy is the mainstay of treatment of malignant pleural mesothelioma (MPM). The European Society for Medical Oncology (ESMO) guidelines, the National Comprehensive Cancer Network (NCCN) guidelines and the European Respiratory Society (ERS) guidelines indicate chemotherapy as an option for patients with 'irresectable MPM' who are not fit for major surgery.[1–3] Only a minority of patients is fit enough to be a surgical candidate and the indication for surgery has become stricter in the last years.

Use of targeted therapy based on genetic profiling has been successful in other solid tumor types, targeting activating oncogenes. In MPM this approach has failed to improve clinical benefit in phase II studies. This is related to the fact that MPM is mostly driven by loss of tumor suppression genes like CDKN2A, NF2 and BAP1, rather than activation of oncogenes.[4] Also, MPM is a heterogeneous tumor type (with three different subtypes) which makes it more challenging to develop effective therapies. Immunotherapy, targeting immune checkpoints (like PD-1 or its ligand PD-L1) has become standard of care in numerous solid tumors like non-small cell lung cancer (NSCLC).[5] The first studies with immunotherapy in second and third- line mesothelioma patients seem promising, but their value in the first line setting has yet not been defined.[6–9] Therefore, chemotherapy remains a prominent treatment option in MPM.

In this review, the current available literature (see Table 1) and ongoing studies (see Table 2) with chemotherapy in the palliative setting and combination strategies in MPM are discussed. The use of chemotherapy as part of multimodality treatment and targeted therapy for MPM is covered in companion papers in this issue.

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