Advances in treatment of mesothelioma

Our plain-English summary of Advances in treatment of mesothelioma, by C. Maggioni, G. Barletta, E. Rijavec, et al (Expert Opinion on Pharmacotherapy, 2016).

The study

• Authors: C. Maggioni, G. Barletta, E. Rijavec, F. Biello, E. Gualco, F. Grossi
• Journal: Expert Opinion on Pharmacotherapy
• Published: 2016;17(9):1197-205
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is an uncommon, aggressive cancer, derived from pleural mesothelial cells, that has a close relationship to asbestos exposure. To date, MPM prognosis is poor and very few treatment options are available for both localized and advanced MPM.

Areas Covered: The standard of care is still chemotherapy with platinum derivates and antifolate agents. In the last few years, several new agents have been studied on the basis of mesothelioma carcinogenesis and invasiveness mechanisms; however, the recent results are poor and few drugs have been tested in phase III trials because of toxicity or because they did not improve patient outcomes. The aim of this review is to focus on the current available treatment for MPM through the analysis of the results comes from the phase III trials and to discuss the future perspectives in the pathogenesis, diagnosis and treatment.

Expert Opinion: Many compounds are currently under investigation in different subsets of patients. Interesting data have come from preliminary studies on immunotherapy, but randomized studies are needed to confirm the preliminary positive results of this new strategy. A better comprehension of MPM pathogenesis should be obtained to improve and develop new diagnostic tools and target therapies.

In plain English

This article reviewed treatments for malignant pleural mesothelioma (MPM), which the authors describe as strongly related to asbestos exposure. It studied no new patients but described published trials of surgery, radiotherapy, chemotherapy and immunotherapy. In a 2003 trial of 448 patients, cisplatin plus pemetrexed gave a median overall survival of 12.1 months, against 9.3 months with cisplatin alone. That combination then became the standard first-line treatment. In the MAPS trial of 445 patients, adding bevacizumab to cisplatin and pemetrexed gave a median overall survival of 18.8 versus 16.1 months. After first-line treatment, vorinostat missed its overall survival end point in a 661-patient trial, and several tyrosine-kinase inhibitors showed no improvement in overall or progression-free survival. The review also noted that CT screening of 1,045 asbestos-exposed workers found no pleural mesothelioma. The authors concluded that no new treatment in ten years had improved survival over platinum and pemetrexed, although elsewhere they called MAPS the first randomized trial in over a decade to show a significant survival improvement. They judged immunotherapy promising but too early to consider.

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 clinical trials and other studies on the diagnosis and treatment of malignant pleural mesothelioma
• Who was studied: No new patients were studied. The review covered published trials and studies in patients with malignant pleural mesothelioma (MPM), with the main first-line and second-line trials listed in two tables.
• Exposure: The review is about treatments for MPM: surgery, radiotherapy, chemotherapy and immunotherapy. Asbestos exposure is discussed only as background on the cause of the disease. The review did not analyze asbestos exposure.
• Main results:
  • As reported by the review, in a phase III trial of 448 MPM patients (Vogelzang et al. 2003), cisplatin plus pemetrexed gave a median overall survival of 12.1 months versus 9.3 months for cisplatin alone (p=0.02).
  • As reported by the review, in the MAPS phase III trial of 445 patients, adding bevacizumab to cisplatin and pemetrexed increased median overall survival from 16.1 to 18.8 months (p=0.012). In their expert opinion section, the authors called MAPS the first randomized trial in over a decade to show a significant improvement in survival in MPM patients.
  • As reported by the review, in a placebo-controlled phase III trial of vorinostat in 661 previously treated patients, the primary end point was not reached. Median overall survival was 30.7 weeks with vorinostat versus 27.1 weeks with placebo.
  • The review stated that none of the trials of tyrosine-kinase inhibitors after first-line treatment showed improvements in overall or progression-free survival. The drugs were imatinib, dasatinib, sorafenib, sunitinib, cediranib, gefitinib and erlotinib.
  • The review stated that pemetrexed, alone or with platinum compounds, is recommended as later treatment for patients who did not receive it first-line. The studies it cited showed increases in response rate, disease control rate and time to progression after pemetrexed. The review also said no standard of care was available for second-line treatment.
  • As reported by the review, in a retrospective study of 663 patients, operative mortality was 7% for extrapleural pneumonectomy (EPP) versus 4% for pleurectomy/decortication (P/D). Overall survival was 16 months for P/D versus 12 months for EPP. The review noted that patient selection could have affected these results.
  • As reported by the review, the MARS randomized trial found no difference between EPP after chemotherapy and chemotherapy alone. The review called these results controversial, partly because only 50 patients were randomized.
  • As reported by the review, in a phase II trial of tremelimumab (an immunotherapy drug) in patients who had progressed after platinum-based chemotherapy, the primary end point was not reached. Disease was controlled in 31% of patients, with 6.2 months of progression-free survival and an overall survival of 10.2 months.
  • The review stated that routine CT screening has not been proven effective for detecting early MPM in workers with occupational asbestos exposure. In one screening cohort of 1,045 asbestos-exposed workers, no case of pleural mesothelioma was detected.
• The authors' conclusion: In their conclusion section, the authors wrote that over the previous ten years no new cytotoxic or biological treatment had improved overall survival compared with or after platinum and pemetrexed, so the standard of care had not changed. Their expert opinion section, however, described the MAPS trial (bevacizumab added to cisplatin and pemetrexed) as the first randomized trial in over a decade to show a significant improvement in survival. They also concluded that immunotherapy showed promising results but that it was too early to consider it.
• Limitations the authors state:
  • The authors stated a limitation of the evidence they reviewed, not of their own review: the roles of surgery and radiotherapy remain debated because adequate clinical trials are lacking.

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: Mesothelioma, Pleural Mesothelioma, Mesothelial Cells, Asbestos Exposure, Prognosis, Chemotherapy, Antifolate, Carcinogenesis.

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