Novel approaches for the treatment of unresectable malignant pleural mesothelioma: A focus on immunotherapy and target therapy (Review)

Our plain-English summary of Novel approaches for the treatment of unresectable malignant pleural mesothelioma: A focus on immunotherapy and target therapy (Review), by E. Rijavec, F. Biello, G. Barletta, et al (Molecular and Clinical Oncology, 2022).

The study

• Authors: E. Rijavec, F. Biello, G. Barletta, C. Dellepiane, C. Genova
• Journal: Molecular and Clinical Oncology
• Published: 2022;16(4):89
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is considered a relatively uncommon disease but its incidence is increasing worldwide. Patients affected by MPM have a very severe prognosis and have been often occupationally and environmentally exposed to asbestos. In recent years, checkpoint inhibitors have dramatically revolutionized the paradigm for the treatment of several malignancies. Several efforts have also been made to improve the survival outcomes of patients with MPM and after decades, the standard-of-care systemic treatment for unresectable MPM, based on first-line combination chemotherapy with cisplatin and pemetrexed, has changed. In addition to checkpoint inhibitors, other types of treatments, such as molecularly targeted therapy have been evaluated. However, to date, the results of these investigations are not very encouraging. The aim of the present review is to provide a comprehensive overview of the most relevant data of clinical trials regarding recent treatment strategies of MPM with a particular focus on immunotherapeutic and targeted approaches.

Copyright © 2020, Spandidos Publications.

In plain English

This article was a review, not a new study. The authors searched PubMed, PMC and NLM databases and major oncology conference abstracts for trials of newer drugs for unresectable malignant pleural mesothelioma, focusing on immune checkpoint inhibitors and targeted agents. Asbestos appeared only as background; the review did not study exposure. In the CheckMate 743 trial, median overall survival was 18.1 months with first-line nivolumab plus ipilimumab versus 14.1 months with chemotherapy (HR 0.74). The CONFIRM trial enrolled patients with pleural or peritoneal mesothelioma after at least two prior lines of therapy; median survival was 10.2 months with nivolumab versus 6.9 months with placebo. PROMISE-meso found no significant survival difference between pembrolizumab and chemotherapy, and in DETERMINE tremelimumab did not improve survival over placebo. Adding bevacizumab to chemotherapy (MAPS) and adding ramucirumab to gemcitabine (RAMES) were reported to lengthen survival. The progression-free survival benefit seen with nintedanib in phase II was not confirmed in phase III. The authors concluded that targeted agents often failed in phase III trials, that immunotherapy had generated fresh optimism, and that predictive biomarkers are still lacking.

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 clinical trials of immune checkpoint inhibitors, targeted agents and CAR-T cell therapy for unresectable malignant pleural mesothelioma
• Who was studied: Published clinical trials and conference abstracts (ESMO, ASCO, IASLC) found through PubMed, PMC and NLM databases. The trials enrolled patients with unresectable malignant pleural mesothelioma, and some also included peritoneal mesothelioma. No search dates or inclusion criteria were stated.
• Exposure: Not an asbestos exposure study. The 'exposures' were the treatments reviewed: checkpoint inhibitors (nivolumab, ipilimumab, durvalumab, pembrolizumab, tremelimumab), anti-angiogenic drugs (bevacizumab, nintedanib, cediranib, ramucirumab), anti-mesothelin drugs (amatuximab, SS1P, anetumab ravtansine) and CAR-T cell therapy. Asbestos was mentioned only as the background cause.
• Main results:
  • CheckMate 743 (605 patients, first-line): median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy (HR 0.74; P=0.002)
  • CheckMate 743 3-year update: 3-year overall survival rate was 23% with nivolumab plus ipilimumab versus 15% with chemotherapy
  • CONFIRM (332 patients with unresectable pleural or peritoneal mesothelioma who had received at least two prior lines of therapy, updated results): median overall survival was 10.2 months with nivolumab versus 6.9 months with placebo (HR 0.69; P=0.009)
  • PROMISE-meso (144 previously treated patients): no significant overall survival difference between pembrolizumab and chemotherapy (10.7 vs. 12.4 months, P=0.59). Objective response rate was higher with pembrolizumab (22% vs. 6%, P=0.004).
  • DETERMINE (pleural or peritoneal mesothelioma after one or two prior chemotherapy treatments): tremelimumab did not improve overall survival compared with placebo (7.7 vs. 7.3 months; HR 0.92; P=0.41)
  • MAPS (448 patients): adding bevacizumab to pemetrexed plus cisplatin significantly improved overall survival (18.8 vs. 16.1 months; HR=0.77)
  • LUME-Meso phase III (458 patients): the progression-free survival advantage for nintedanib seen in phase II was not confirmed (6.8 vs. 7.0 months; HR=1.01)
  • RAMES (161 patients, second-line): ramucirumab plus gemcitabine gave longer overall survival than gemcitabine alone (13.8 vs. 7.5 months; HR=0.71)
  • Anetumab ravtansine was not superior to vinorelbine for median progression-free survival (4.3 vs. 4.5 months; HR=1.215) in previously treated patients with mesothelin over-expressing tumors
• The authors' conclusion: The authors concluded that targeted agents often failed in phase III trials, probably because the patients who might benefit could not be identified. They wrote that checkpoint inhibitor immunotherapy has generated fresh optimism, and that CheckMate 743 changed the first-line standard of care.
• Limitations the authors state:
  • The authors noted that CheckMate 743 was not powered to detect differences between epithelioid and non-epithelioid subgroups
  • The authors cautioned that the CheckMate 743 finding of a chemotherapy survival benefit in patients with PD-L1 below 1% was exploratory
  • The authors stated that suitable predictive biomarkers for patient selection are still lacking

Topics

Medical terms in this study, explained in our Lexicon: Unresectable, Pleural Mesothelioma, Immunotherapy, Prognosis, checkpoint inhibitors, Chemotherapy, Cisplatin, Pemetrexed (Alimta).

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