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

Our plain-English summary of Systemic therapy options for malignant pleural mesothelioma beyond first-line therapy: a systematic review, by O. Abdel-Rahman, M. Kelany (Expert Review of Respiratory Medicine, 2015).

The study

• Authors: O. Abdel-Rahman, M. Kelany
• Journal: Expert Review of Respiratory Medicine
• Published: 2015;9(5):533-49
• Type of article: Systematic review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This systematic review covered drug treatments for malignant pleural mesothelioma after earlier treatment failed. The authors included 29 studies (2321 patients): 3 Phase III, 18 Phase II and 8 retrospective. No Phase III trial showed an overall survival benefit. Vorinostat versus placebo gave an overall survival hazard ratio of 0.98 (95% CI 0.83 to 1.17). In patients not given pemetrexed first-line, median survival was 8.4 months with pemetrexed versus 9.7 with best supportive care (p = 0.7). With both groups getting the investigator's choice of chemotherapy or supportive care, median survival was 8.4 months with NGR-hTNF versus 7.9 with placebo (p = 0.61). Most Phase II trials did not justify Phase III testing. Disease control rates were 10 to 81% (Phase II) and 43 to 82% (retrospective). Noted limitations were varied regimens and missing biomarker studies. The authors concluded a clinical trial is best. Otherwise, gemcitabine and/or vinorelbine could be considered in patients with good performance status despite low evidence of benefit. On retrospective evidence, pemetrexed re-challenge could be considered in pemetrexed-sensitive patients with a long treatment-free interval after initial pemetrexed-based therapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: systematic review of clinical studies (Phase III, Phase II and retrospective studies) found in databases and meeting abstracts
• Who was studied: 29 studies involving a total of 2321 patients with advanced malignant pleural mesothelioma who had received prior systemic therapy; literature searched up to May 2015
• Exposure: Salvage (second- or third-line) systemic drug treatments for advanced malignant pleural mesothelioma, including vorinostat, pemetrexed, NGR-hTNF, tremelimumab, gemcitabine and vinorelbine; asbestos exposure was not studied
• Main results:
  • Phase III trial (Krug et al., 661 patients), vorinostat versus placebo: progression-free survival hazard ratio 0.75 (95% CI 0.63 to 0.88); overall survival not different, hazard ratio 0.98 (95% CI 0.83 to 1.17)
  • Phase III trial (Jassem et al., 243 patients who had not received pemetrexed-based first-line regimens), pemetrexed versus best supportive care: median overall survival 8.4 versus 9.7 months (p = 0.7); progression-free survival 3.6 versus 1.5 months (p = 0.014)
  • Phase III trial (Gaafar et al., 400 patients, reported as a meeting abstract): weekly NGR-hTNF versus placebo, both given with the investigator's choice of gemcitabine, vinorelbine, doxorubicin or supportive care. Median overall survival was 8.4 versus 7.9 months (hazard ratio 0.94, p = 0.61).
  • None of the three Phase III studies reported improved overall survival
  • Most Phase II studies did not give results good enough to justify moving on to Phase III trials
  • Disease control rate ranged from 10 to 81% in the second-line Phase II studies and from 43 to 82% in the 8 retrospective studies
  • In the retrospective studies, the outcome of pemetrexed re-challenge was described as better, particularly in patients with a longer progression-free period after first pemetrexed therapy
  • Most reported side effects were grade 1 to 2 and tolerable
  • Biomarker research in the included trials found no reliable predictive marker
• The authors' conclusion: The authors concluded that the best salvage treatment is taking part in a clinical trial. Without a trial, gemcitabine and/or vinorelbine-based regimens could be considered in patients with good performance status, despite low evidence of benefit. Based on retrospective evidence, pemetrexed re-challenge could be considered in appropriately selected pemetrexed-sensitive patients with a long treatment-free interval after initial pemetrexed-based therapy.
• Limitations the authors state:
  • The regimens used varied widely between studies, and patients were at different disease stages
  • Most included studies lacked proper biomarker studies, so the role of disease biology in the negative findings could not be assessed
  • Some included studies did not evaluate quality of life and symptom scores

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Systemic Therapy, Pleural Mesothelioma, First-line Therapy, Systematic Review, Overall Survival, Clinical Trial, Gemcitabine, Vinorelbine.

Related studies

• Pemetrexed re-challenge in pleural malignant mesothelioma: an option for a subset of patients initially treated with pemetrexed-platinum doublets in the first-line setting? — G. Zalcman, E. Bergot, et al. (2011)
• Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review — X.Q. Jing, L. Zhou, et al. (2016)
• Fibrinogen concentrate as first-line therapy in children undergoing cardiac surgery: Promising perspectives — D. Faraoni (2015)
• Second line therapy in malignant pleural mesothelioma: A systematic review — W.A. Buikhuisen, B.I. Hiddinga, et al. (2015)
• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• Novel and Future Treatment Options in Mesothelioma: A Systematic Review — D. Štrbac, V. Dolžan (2022)

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