Updates in the diagnosis and treatment of malignant pleural mesothelioma

Our plain-English summary of Updates in the diagnosis and treatment of malignant pleural mesothelioma, by D. Katzman, D.H. Sterman (Current Opinion in Pulmonary Medicine, 2018).

The study

• Authors: D. Katzman, D.H. Sterman
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2018;24(4):319-326
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: This review article describes current diagnostic and treatment modalities for malignant pleural mesothelioma (MPM).

Recent Findings: Few randomized trials in MPM have demonstrated improved survival with current therapies. A randomized trial of first-line chemotherapy with and without bevacizumab in unresectable MPM is the only randomized trial of a new treatment regimen to demonstrate a survival benefit since cisplatin with pemetrexed became the standard of care for unresectable MPM in 2003. Unfortunately, in unresectable MPM, first-line chemotherapy alone or in combination with bevacizumab has demonstrated only limited improvements in overall survival. Recently, in nonrandomized observational studies, multimodality treatments with chemotherapy, surgery, radiation, and novel therapies have been associated with prolonged survival in select patients. Currently, there are no FDA approved second-line therapies, and clinical trial enrollment is recommended for second-line treatment.

Summary: MPM remains difficult to treat and has an overall poor prognosis despite current multimodality treatment. Thoracoscopy with multiple pleural biopsies can provide adequate tissue specimens for diagnostic testing to distinguish histologic MPM subtypes and perform molecular profiling, which influence prognosis and treatment options. In early clinical trials, immunotherapies and therapies directed against cancer-associated antigens and oncogenic alterations are emerging as promising future treatments.

In plain English

This was a review article, not a new study, describing how malignant pleural mesothelioma (MPM) is diagnosed and treated. It summarized earlier published trials and database analyses. Citing other work, the authors noted that around 70% of MPM develops from documented asbestos exposure. They described pleural fluid cytology as having low diagnostic sensitivity, and thoracoscopy with multiple pleural biopsies as the recommended approach. In a National Cancer Data Base analysis they cited, median survival was 4.8, 11.3, 15.3 and 19.9 months with no therapy, chemotherapy alone, chemotherapy and surgery, and trimodality therapy. In cited randomized trials, adding pemetrexed to cisplatin improved median overall survival from 9.3 to 12.1 months, and adding bevacizumab to cisplatin and pemetrexed improved it from 16.1 to 18.8 months. They reported that no randomized trial has shown a survival benefit from multimodality treatment including surgery. They also reported that, in the DETERMINE trial, tremelimumab did not improve overall survival compared with placebo. The authors concluded that poor survival persists despite current standard multimodality treatment and that novel therapies are needed.

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 diagnosis and treatment of malignant pleural mesothelioma
• Who was studied: No study population of its own; the review summarized published clinical trials, database analyses and other studies of malignant pleural mesothelioma, with key trials listed in a table
• Exposure: Asbestos exposure was not studied. The review covered diagnostic tests and treatments (chemotherapy, surgery, radiation, immunotherapy, targeted therapies). As background, citing earlier work, it stated that around 70% of MPM develops from documented asbestos exposure, usually after a 30 to 40 year latency. No fiber types were named.
• Main results:
  • Citing earlier work, the review stated that pleural fluid cytology has low diagnostic sensitivity and cannot identify MPM subtypes. It said thoracoscopy with multiple pleural biopsies is recommended.
  • In a cited National Cancer Data Base analysis (2003 to 2014, more than 19,000 MPM cases), median survival was 4.8, 11.3, 15.3 and 19.9 months for no therapy, chemotherapy alone, chemotherapy and surgery, and trimodality therapy including radiation, respectively.
  • In a cited phase III randomized trial in treatment-naive, unresectable MPM, cisplatin with pemetrexed, compared with cisplatin alone, improved response rates from 16.7 to 41.3%. It also prolonged median overall survival from 9.3 to 12.1 months.
  • In a cited phase III randomized trial in unresectable MPM, adding bevacizumab to cisplatin and pemetrexed prolonged median overall survival from 16.1 to 18.8 months.
  • The review stated that no randomized trial has shown a survival benefit with multimodality treatment including surgery versus nonsurgical interventions.
  • In a cited phase III randomized trial, prophylactic radiation therapy to incision sites after pleural procedures, compared with deferred radiation therapy, showed no difference in procedure-tract metastasis. The table gives 9% versus 16%, P = 0.14.
  • In the cited DETERMINE trial (571 pleural and peritoneal mesothelioma patients), second-line or third-line tremelimumab did not improve overall survival compared with placebo.
  • In the cited KEYNOTE 28 trial of 25 previously treated MPM patients with tumor PD-L1 expression of at least 1%, pembrolizumab gave an overall response rate of 20%. The disease control rate was 72%.
  • In the cited IFCT-1501 MAPS 2 trial of 125 MPM patients, there were no significant differences between nivolumab and nivolumab plus ipilimumab. Overall response rates were 18.5 versus 27.8%, disease control rates 44.4 versus 50.0%, and 12-month overall survival 51 versus 58%.
  • In a cited trial of MPM patients with ASS1 deficiencies, adding arginine deprivation with pegylated arginine deaminase to standard treatment improved progression-free survival, 3.2 versus 2.0 months.
• The authors' conclusion: The authors concluded that poor survival in MPM persists despite current standard multimodality treatment, that novel therapies are needed, and that identifying MPM-specific mutations and other targets provides hope for improved survival and quality of life.

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, Chemotherapy, Bevacizumab, Unresectable, Cisplatin, Pemetrexed (Alimta), Overall Survival, Clinical Trial.

Related studies

• Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up — R.A. Stahel, W. Weder, et al. (2010)
• Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies — A.R. Haas, D.H. Sterman (2013)
• The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan — T. Kitai (2021)
• Malignant pleural mesothelioma: an update on diagnosis and treatment options — S. Kondola, D. Manners, et al. (2016)
• SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020) — E. Nadal, J. Bosch-Barrera, et al. (2021)
• Recent advances in the treatment of malignant pleural mesothelioma — S.S. Ramalingam, C.P. Belani (2008)

Browse more research in Current Opinion in Pulmonary Medicine, or return to medical research.