Advances in the systemic therapy of malignant pleural mesothelioma

Our plain-English summary of Advances in the systemic therapy of malignant pleural mesothelioma, by D.A. Fennell, G. Gaudino, K.J. O'Byrne, et al (Nature Clinical Practice. Oncology, 2008).

The study

• Authors: D.A. Fennell, G. Gaudino, K.J. O'Byrne, L. Mutti, J. van Meerbeeck
• Journal: Nature Clinical Practice. Oncology
• Published: 2008;5(3):136-47
• Type of article: Review
• Cited by: 112 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

In plain English

This article was a review, not new research. The authors searched PubMed and MEDLINE for English-language articles to 1 September 2007 on malignant pleural mesothelioma (an asbestos-associated cancer), including trials, prognosis, biomarkers and PET imaging. Across 59 trials the average response rate was 15.7%, and platinum-based regimens had higher response rates than non-platinum regimens (24% vs 8%). In one of two randomized phase III trials described, median overall survival was 12.1 months with pemetrexed plus cisplatin (226 patients) versus 9.3 months with cisplatin alone (222 patients). In the other, it was 11.4 months with raltitrexed plus cisplatin (126 patients) versus 8.8 months with cisplatin alone (124 patients). In previously treated patients, a phase III trial found adding pemetrexed to supportive care did not significantly increase overall survival. The authors concluded that antifolate–platinum combinations were the standard first-line chemotherapy for patients with good performance status and unresectable disease, but that the results could not be extended to insufficiently studied groups such as patients over 75. They cautioned that older trials differ widely and single-arm trials are open to bias.

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: Narrative review of published literature on systemic (drug) therapy, prognostic factors and new treatments for malignant pleural mesothelioma
• Who was studied: Published English-language articles found in PubMed and MEDLINE up to 1 September 2007 on mesothelioma. Search terms covered clinical trials, biomarkers, gene expression profiling, prognosis, tumor markers and PET. The articles concerned patients with malignant pleural mesothelioma.
• Exposure: Not an exposure study. The review concerns chemotherapy and other drug treatments, prognosis and imaging. Asbestos is mentioned only as associated with the disease.
• Main results:
  • Across 59 published trials conducted over 30 years, the average response rate was 15.7%.
  • In the same series of 59 published trials, response rates were 24% for platinum-containing regimens versus 8% for non-platinum regimens.
  • Across the trial series, median survival was 10 months with combination therapy versus 8.1 months with single-agent therapy. The authors described this improvement as less impressive than the difference in response rates.
  • Patient numbers in the two phase III trials summarized in Table 2: Vogelzang et al., 222 on cisplatin alone and 226 on pemetrexed–cisplatin; van Meerbeeck et al., 124 on cisplatin alone and 126 on raltitrexed–cisplatin.
  • Response rates (95% CI) in the two phase III trials: 17% (12–22) with cisplatin alone versus 41% (35–48) with pemetrexed–cisplatin; 14% (7–20) with cisplatin alone versus 24% (16–32) with raltitrexed–cisplatin.
  • Median overall survival in the two phase III trials: 9.3 months with cisplatin alone versus 12.1 months with pemetrexed–cisplatin; 8.8 months with cisplatin alone versus 11.4 months with raltitrexed–cisplatin.
  • Hazard ratios for overall survival compared with cisplatin alone: 0.77 (95% CI 0.60–0.90; P = 0.002) for pemetrexed–cisplatin, and 0.76 (95% CI 0.58–1.00; P = 0.048) for raltitrexed–cisplatin.
  • In a phase III trial in previously treated (second-line) patients, pemetrexed with vitamin supplementation and best supportive care was compared with best supportive care alone. Response rate and progression-free survival increased with pemetrexed, but overall survival was not increased significantly.
  • Under the EORTC prognostic scoring system, median survival was 10.8 months in the low-risk group versus 5.5 months in the high-risk group.
• The authors' conclusion: The authors concluded that two randomized trials established antifolate–platinum doublets as a widely adopted standard first-line treatment for inoperable malignant pleural mesothelioma. More specifically, they regarded cisplatin with an antifolate as the standard chemotherapy for patients with good performance status and unresectable disease. They also concluded that reliable predictive biomarkers are not yet in routine clinical practice.
• Limitations the authors state:
  • The authors stated that results of older studies require cautious interpretation, because those studies differ widely in trial design, patient selection, response criteria, sample size and power.
  • Only English-language articles were included in the review.
  • The authors noted that the effect of clinical prognostic factors on outcome means single-arm phase II trials have potential for considerable bias.
  • The authors stated that the phase III results cannot be extended to insufficiently studied subgroups: patients with moderate or poor performance status, the elderly (over 75 years), and patients with the sarcomatous histologic subtype.

Topics

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

Medical terms in this study, explained in our Lexicon: Systemic Therapy, Pleural Mesothelioma, Chemotherapy, Clinical Trial, Mesothelioma.

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