Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials

Our plain-English summary of Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials, by A.S. Mansfield, J.T. Symanowski, T. Peikert (Lung Cancer, 2014).

The study

• Authors: A.S. Mansfield, J.T. Symanowski, T. Peikert
• Journal: Lung Cancer
• Published: 2014;86(2):133-6
• Type of article: Meta-analysis, Systematic review
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Rationale: Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes.

Objectives: Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials.

Methods: We searched PubMed for "mesothelioma" with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors.

Measurements And Main Results: We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review.

Conclusion: Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In plain English

This was a systematic review of published clinical trials of drug treatments for malignant pleural mesothelioma, a cancer the authors describe as primarily related to asbestos exposure. Asbestos exposure itself was not studied. The authors searched PubMed for trials published from January 1, 2000 to March 20, 2014 that gave first- or second-line systemic therapy. Trials of combined treatment that included surgery were excluded. Of 41 trials that met the criteria, 11 included no patients with the sarcomatoid subtype. The remaining 30 trials included 1475 subjects, of whom 137 (9.3%) had sarcomatoid tumors. Across all subtypes, 323 subjects had a complete or partial response, an overall response rate of 21.9% (95% CI 16.3 to 28.8). Among the 137 sarcomatoid patients, 19 responded, a response rate of 13.9% (95% CI 8.6 to 21.6). The authors concluded that response rates by subtype are reported in a minority of publications and that responses appear less common in sarcomatoid tumors. They noted that multiple biases likely affected the review, including the lack of central review of tumor subtypes and differing ways of measuring response.

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 published clinical trials (response rates pooled using a logistic regression model allowing for variation between trials)
• Who was studied: Clinical trials of systemic therapy for malignant pleural mesothelioma published January 1, 2000 to March 20, 2014 and found on PubMed. 41 trials met the criteria; 30 trials with 1475 subjects were analysed.
• Exposure: First- or second-line systemic (drug) therapies for malignant pleural mesothelioma. Asbestos exposure was not analysed; it is mentioned only as the main cause of the disease.
• Main results:
  • Of 41 eligible trials, 11 did not include any patients with sarcomatoid mesothelioma.
  • Of the 1475 subjects in the 30 analysed trials: 1011 had epithelioid tumors (68.5%), 203 biphasic (13.8%), 137 sarcomatoid (9.3%) and 124 unknown subtype (8.4%).
  • All subtypes combined: 323 complete or partial responses, an overall response rate of 21.9% (95% CI 16.3 to 28.8).
  • Sarcomatoid tumors: 19 responses among 137 patients, a response rate of 13.9% (95% CI 8.6 to 21.6). These made up 5.9% of all responses.
  • Sarcomatoid tumors treated with first-line therapy: 18 of the 19 responses, a first-line response rate of 16.7% (95% CI 9.7 to 27.2).
  • Sarcomatoid tumors in the complementary group of trials (those not limited to first-line therapy): response rate 3.5% (95% CI 0.5 to 20.8).
  • Sarcomatoid subjects in the phase III cisplatin and pemetrexed trial (subtype data obtained from that trial's authors): overall response rate 22.2% (95% CI 6.4 to 47.6) among 18 subjects. By comparison, the rate was 41.3% among the 225 subjects in that trial who had measurable disease.
  • Sarcomatoid subjects by type of regimen: 4 of 30 (13%) treated with pemetrexed-based regimens responded, compared with 15 of 107 (14%) treated with non-pemetrexed-based regimens.
• The authors' conclusion: The authors concluded that response rates by mesothelioma subtype are reported in a minority of publications, that fewer responses are seen in subjects with sarcomatoid tumors, and that therapy based on histological subtype should be considered for future clinical trials.
• Limitations the authors state:
  • Only a minority of trials reported responses by subtype.
  • 8.4% of subjects had unknown subtypes, and their response rates were almost never reported separately.
  • Data on demographics, stable disease, progression-free survival and overall survival by subtype could not be extracted from all but a few publications.
  • Because of sampling error, some biphasic tumors may have been diagnosed as epithelioid or sarcomatoid.
  • There was no central review of histologic subtypes in the included studies.
  • The reported responses could not be confirmed.
  • The trials used different ways of measuring response.
  • The authors suspected some publication bias, with some trials showing no activity possibly unpublished.
  • No risk-of-bias assessment was done, because most included studies were not randomized.

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, Sarcomatoid, Pleural Mesothelioma, Clinical Trial, Asbestos Exposure, Histological Subtype, Mesothelioma, Histology.

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