Second line therapy in malignant pleural mesothelioma: A systematic review

Our plain-English summary of Second line therapy in malignant pleural mesothelioma: A systematic review, by W.A. Buikhuisen, B.I. Hiddinga, P. Baas, et al (Lung Cancer, 2015).

The study

• Authors: W.A. Buikhuisen, B.I. Hiddinga, P. Baas, J.P. van Meerbeeck
• Journal: Lung Cancer
• Published: 2015;89(3):223-31
• Type of article: Meta-analysis, Systematic review
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

After the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In plain English

This article was a systematic review of earlier trials. The authors updated an earlier review of 'second line' drug treatment for malignant pleural mesothelioma that had relapsed or progressed after first-line chemotherapy. They looked for prospective phase II and III trials published in English between January 2000 and July 2014. Ten chemotherapy articles, covering 1251 patients, were eligible. In the phase III trial of second-line pemetrexed versus best supportive care, response rates were 19.2% and 1.7%. Median time to progression was 3.8 versus 1.5 months. Median overall survival was 8.6 versus 9.8 months, which was not significantly different. Anti-angiogenic drugs reported low response rates. A tremelimumab trial in 29 patients did not meet its primary endpoint, but disease control was seen in 9 patients (31%). The authors concluded that single agent vinorelbine or pemetrexed are acceptable second line agents after a first line platinum combination, depending on whether it included pemetrexed. They also concluded that the low activity of second line drugs warrants referring fit patients to clinical trials. They noted selection bias in some of the data they reviewed. The review did not study asbestos exposure.

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 (an update of an earlier systematic review) of prospective phase II and phase III trials of second line treatment
• Who was studied: Published prospective trials in patients with malignant pleural mesothelioma (MPM), in English, January 2000 to July 2014, plus conference abstracts from 2010 to 2014. Ten eligible chemotherapy articles reported on 1251 patients. The number of targeted-agent studies is in a table that is not included in the text.
• Exposure: No asbestos exposure was studied. The review covered drug treatments given after first-line chemotherapy: chemotherapy (e.g. pemetrexed, vinorelbine, picoplatin, gemcitabine/docetaxel, raltitrexed/oxaliplatin, valproic acid/doxorubicin) and targeted or biological agents (e.g. everolimus, anti-angiogenic drugs, NGR-hTNF, tremelimumab, pembrolizumab, SS1P, bortezomib).
• Main results:
  • The phase III trial of second-line pemetrexed versus best supportive care enrolled patients who had relapsed after first-line chemotherapy that did not include pemetrexed.
  • In that phase III trial (243 patients), the response rate was 19.2% in the pemetrexed group versus 1.7% in the best supportive care group.
  • In the same phase III trial, median time to progression was 3.8 months with pemetrexed versus 1.5 months with best supportive care.
  • In the same phase III trial, median overall survival was 8.6 months with pemetrexed versus 9.8 months with best supportive care, a difference that was not statistically significant.
  • In a phase II trial of weekly vinorelbine, 16% of 63 pre-treated patients had a partial response.
  • Over half of the patients in the vinorelbine trial had a grade 3/4 toxicity.
  • Phase II studies of anti-angiogenic drugs (sorafenib, sunitinib, vatalanib, cediranib) reported low response rates.
  • In a single arm phase 2 study of tremelimumab in 29 patients, the primary endpoint was not met. Disease control was observed in 9 patients (31%).
  • Pembrolizumab, reported only in a conference abstract, gave an overall response rate of 20% and disease control in 72% in a group of 25 patients with PD-L1 positive staining.
• The authors' conclusion: The authors concluded that single agent vinorelbine or pemetrexed are acceptable second line agents for patients relapsing after a first line platinum combination, with the choice depending on whether that combination included pemetrexed. They also concluded that the low reported activity of second line drugs warrants referral of fit patients to clinical trials, and that immune checkpoint inhibitors and immunotoxins seem more effective.
• Limitations the authors state:
  • The authors noted that the post-study chemotherapy data from the pivotal phase III trial had important limitations due to selection bias, because patients receiving second-line chemotherapy were a selected group in good clinical condition.
  • The authors noted bias in the expanded access program data, because its inclusion criteria were less stringent than those of a formal clinical trial.
  • The authors noted that the number of patients with MPM who are suitable candidates for studies is relatively small.

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: Pleural Mesothelioma, Systematic Review, Chemotherapy, Antifolate.

Related studies

• A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma — F. Petrelli, R. Ardito, et al. (2018)
• Phase II trial of ZD0473 as second-line therapy in mesothelioma — G. Giaccone, M.E. O'Brien, et al. (2002)
• Pemetrexed for malignant pleural mesothelioma: Is it a standard second-line therapy? — K. Tamura, Y. Fujiwara (2010)
• Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma — M.G. Zauderer, S.L. Kass, et al. (2014)
• A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma — A.K. Nowak, M.J. Millward, et al. (2012)
• A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma — W.S. Lam, J. Creaney, et al. (2020)

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