A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma

Our plain-English summary of A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma, by F. Petrelli, R. Ardito, B. Conti, et al (Respiratory Medicine, 2018).

The study

• Authors: F. Petrelli, R. Ardito, B. Conti, A. Coinu, M. Cabiddu, M. Ghilardi, K. Borgonovo, S. Barni, A. Ghidini
• Journal: Respiratory Medicine
• Published: 2018;141:72-80
• Type of article: Meta-analysis, Systematic review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Advanced malignant pleural mesothelioma (MPM) is generally treated with platinum/pemetrexed-based first-line therapy. Once the disease progresses, evidence for the efficacy of palliative treatments is lacking, and platinum re-challenge or single-agent chemotherapy are commonly used. To assess the effects of cytostatic or targeted therapy for treating MPM, we performed a systematic review and meta-analysis.

Material And Methods: PubMed, the Cochrane Library, and Embase databases were searched to identify published articles on second-line treatments for recurrent or advanced mesothelioma. Inclusion criteria were publication in the English language, describing clinical trials with 20 or more patients, and evaluability for efficacy and for receiving second-line systemic therapies. Data were pooled using number of events/number of evaluable patients, median overall survival (OS) and progression-free survival (PFS), according to a fixed or random effect model. Pooled median OS was the primary endpoint.

Results: A total of 49 eligible studies (n = 3938 patients; range, 12-400) were identified. Median progression-free survival (PFS) was 3.4 months (95%CI 2.87-3.93). Median pooled OS was 7.86 (95%CI 7.01-8.72). The pooled overall response rate (ORR) was 8.63% (95%CI 6-11.26), and the pooled disease control rate (DCR) was 54.8% (95%CI 48.9-60.6). Median pooled OS with platinum- and pemetrexed-based chemotherapy were 7.93 and 7.78 months, respectively.

Conclusions: There remains uncertainty about the ideal second-line agent for MPM. Based on this meta-analysis, palliative chemotherapy or other experimental agents can be considered for patients with MPM who desire further treatment after their disease has progressed, during or after first-line therapy.

Copyright © 2018. Published by Elsevier Ltd.

In plain English

This was a systematic review and meta-analysis of earlier studies; the authors treated no patients themselves. The authors searched three databases for studies of second-line treatment, given after first-line therapy, for recurrent or advanced mesothelioma, mostly malignant pleural mesothelioma. They included 49 studies with 3938 patients, published 2005 to 2018. The treatments were chemotherapy, targeted therapies and immunotherapies. Pooled median overall survival was 7.86 months (95% CI 7.01 to 8.72), and median progression-free survival was 3.4 months (95% CI 2.87 to 3.93). The pooled response rate was 8.63% (95% CI 6 to 11.26) and the disease control rate 54.9% (95% CI 49.3 to 60.4). Immunotherapy showed a non-significant trend toward longer survival than targeted therapy or chemotherapy (10.75 vs 7.32 vs 8.35 months; P = 0.18). Survival did not improve over the years studied. The authors concluded that second-line therapy is moderately effective and outcomes have not changed in the past decade. They noted that only three studies were randomised, treatments and patients varied widely, results differed greatly between studies, and there were signs of publication bias. Asbestos exposure was not studied.

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 and meta-analysis of published clinical studies (phase 1b, 2 and 3 trials, expanded access programmes, observational studies and retrospective series)
• Who was studied: 49 studies totalling 3938 patients (study sizes 12 to 400) with recurrent or advanced mesothelioma, mostly malignant pleural mesothelioma, who received second-line therapy. Studies were published 2005 to 2018. All but one study (a Chinese population) were described as Caucasian patients treated in Western countries.
• Exposure: No asbestos exposure was studied. The 'exposure' was second-line systemic treatment: chemotherapy regimens (for example pemetrexed, platinum drugs, gemcitabine, vinorelbine), targeted therapies, and immunotherapies (tremelimumab, pembrolizumab).
• Main results:
  • Pooled median overall survival across 41 studies was 7.86 months (95% CI 7.01 to 8.72), with high heterogeneity between studies.
  • Pooled median progression-free survival across 40 studies was 3.4 months (95% CI 2.87 to 3.93).
  • Pooled overall response rate (40 studies) was 8.63% (95% CI 6 to 11.26), and pooled disease control rate (42 studies) was 54.9% (95% CI 49.3 to 60.4).
  • In a sub-group analysis, median overall survival was 10.75 months with immunotherapy, 7.32 months with targeted therapies and 8.35 months with chemotherapies. The authors called this a trend; the difference was not statistically significant (P = 0.18).
  • Median pooled overall survival was 7.93 months with platinum-based chemotherapy and 7.78 months with pemetrexed-based chemotherapy.
  • In meta-regression, overall survival did not improve from 2005 to 2017 (P = 0.41).
  • Begg's and Egger's tests showed evidence of some publication bias (P = 0.005 for both).
• The authors' conclusion: The authors concluded that second-line therapy for malignant mesothelioma after platinum-based treatment is moderately effective, with median overall survival of about 8 months, a modest response rate and median progression-free survival of 3.4 months. They concluded that outcomes have not improved over the past decade.
• Limitations the authors state:
  • Only three randomised studies were included, so any added benefit of second-line therapy could not be defined.
  • The included studies used different regimens and enrolled patients with different disease statuses, comorbidities and disease burdens.
  • Heterogeneity between studies was high, and there was evidence of publication bias.
  • Effectiveness by time to progression on first-line therapy and by tumour histology could not be calculated, because too few studies reported these data.

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: Systematic Review, Meta-Analysis, Mesothelioma, Pleural Mesothelioma, Pemetrexed (Alimta), First-line Therapy, Palliative Care, Chemotherapy.

Related studies

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• Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial — M. Maio, A. Scherpereel, et al. (2017)
• Pemetrexed for malignant pleural mesothelioma: Is it a standard second-line therapy? — K. Tamura, Y. Fujiwara (2010)
• A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma — C. Cao, D. Tian, et al. (2014)
• Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial — C. Pinto, P.A. Zucali, et al. (2021)
• A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma — A.K. Nowak, C. Brown, et al. (2013)

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