Systemic therapy options for malignant pleural mesothelioma beyond first-line therapy: a systematic review

Abstract

The aim of this systematic review is to assess the evidence for the available 2nd/3rd line systemic therapies for malignant pleural mesothelioma (MPM). Eligible studies were obtained through appropriate databases and meetings abstracts search. A total of 29 studies were considered eligible for this review and it includes three Phase III studies, eighteen phase II studies and eight retrospective studies. For the Phase III studies, none have achieved an overall survival benefit; while for the Phase II studies, the majority have not achieved sufficient satisfactory outcome to justify advancement to Phase III studies. We believe that the best salvage treatment for MPM would be inclusion into appropriately designed clinical trials. In the absence of a clinical trial, gemcitabine and/or vinorelbine-based regimens could be considered. Moreover, pemetrexed re-challenge can be considered in selected pemetrexed-sensitive patients.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016

“…48,56,57 New agents are being assessed in the frontline setting for MPM. 43,[58][59][60][61] A recent multicenter phase III randomized trial assessed the addition of bevacizumab to cisplatin/ pemetrexed (with maintenance bevacizumab) compared with cisplatin/pemetrexed alone for patients 75 years of age or younger with unresectable MPM and PS 0 to 2 who did not have significant cardiovascular history, including history of stroke or transient ischemic attack. 47 Most patients (97%) were PS 0 to 1.…”

“…Recommended second-line chemotherapy options include pemetrexed (if not administered firstline) (category 1), vinorelbine, or gemcitabine (see MPM-B, page 828). 57,58,[62][63][64][65][66][67] If patients experienced a good response to first-line pemetrexed, data suggest that repeating pemetrexed is effective, especially in those who achieved a treatment-free interval of at least 3 months. 58,[68][69][70] Several agents are in clinical trials.…”

“…57,58,[62][63][64][65][66][67] If patients experienced a good response to first-line pemetrexed, data suggest that repeating pemetrexed is effective, especially in those who achieved a treatment-free interval of at least 3 months. 58,[68][69][70] Several agents are in clinical trials. 58,61,68,[71][72][73] Preliminary data suggest that immune checkpoint inhibitors and agents targeting mesothelin may be useful in MPM.…”

“…58,[68][69][70] Several agents are in clinical trials. 58,61,68,[71][72][73] Preliminary data suggest that immune checkpoint inhibitors and agents targeting mesothelin may be useful in MPM. [74][75][76][77][78][79]…”

Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

“…Nevertheless, MPM is often refractory to chemotherapeutic agents, and treatment intent is mostly palliative. 5, 6, 7 …”