Contemporary management of mesothelioma

Our plain-English summary of Contemporary management of mesothelioma, by M.D.J. Neilly, J. Pearson, A.W. Thu, et al (Breathe, 2024).

The study

• Authors: M.D.J. Neilly, J. Pearson, A.W. Thu, C. MacRae, K.G. Blyth
• Journal: Breathe
• Published: 2024;20(2):230175
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is an aggressive asbestos-associated thoracic malignancy with a median survival of 12-18 months. Due to continued asbestos use in many nations, global incidence is rising. Causes due to non-occupational, environmental exposure are also rising in many countries despite utilisation bans. For many years, platinum--pemetrexed chemotherapy was the solitary licensed therapy, but first-line combination immune checkpoint blockade has recently demonstrated improved outcomes, with both regimes tested in predominantly late-stage cohorts. In the second-line setting, single-agent nivolumab has been shown to extend survival and is now available for routine use in some regions, while second-line chemotherapy has no proven role and opportunities for clinical trials should be maximised in relapsed disease. Surgery for "technically resectable" disease has been offered for decades in many expert centres, but the recent results from the phase III MARS2 trial have challenged this approach. There remains no robustly proven standard of care for early-stage PM. The clinical trial landscape for PM is complex and increasingly diverse, making further development of specialist PM multidisciplinary teams an important priority in all countries. The observation of improving outcomes in centres that have adopted this service model emphasises the importance of high-quality diagnostics and equitable access to therapies and trials. Novel therapies targeting a range of aberrations are being evaluated; however, a better understanding of the molecular drivers and their associated vulnerabilities is required to identify and prioritise treatment targets.

Copyright ©ERS 2024.

In plain English

This article was a narrative review, not a new study. The authors summarised current treatment of pleural mesothelioma, which they described as causally linked to prior asbestos exposure in most patients. They reviewed published trials of surgery, chemotherapy, immunotherapy and radiotherapy. Among the results they cited: in the CheckMate743 trial, median overall survival was 18.1 months (95% CI 16.8–21.4) with ipilimumab plus nivolumab versus 14.1 months (95% CI 12.4–16.2) with cisplatin-pemetrexed chemotherapy (hazard ratio 0.74, p=0.002). In the CONFIRM trial in relapsed disease, overall survival was 10.2 months with nivolumab versus 6.9 months with placebo. Conference reports of the MARS2 trial, not yet fully published, described increased mortality and reduced quality of life with surgery plus chemotherapy compared with chemotherapy alone. The authors concluded that ipilimumab plus nivolumab had become standard first-line care for most patients with later-stage, "unresectable" disease. They also stated that early-stage disease had no proven standard of care and that second-line chemotherapy had no proven role. They noted that both main first-line drug regimens were tested mostly in patients with advanced disease.

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 the management of pleural mesothelioma
• Who was studied: No study population of its own. The review covers published evidence on patients with pleural mesothelioma, mainly clinical trials of surgery, systemic therapies and radiotherapy.
• Exposure: Asbestos exposure was not studied. The review describes pleural mesothelioma as causally linked to prior asbestos exposure in most patients and does not discuss specific fiber types.
• Main results:
  • Cited CheckMate743 trial (605 patients with unresectable pleural mesothelioma): median overall survival was 18.1 months (95% CI 16.8–21.4) with ipilimumab/nivolumab versus 14.1 months (95% CI 12.4–16.2) with cisplatin/pemetrexed; hazard ratio 0.74, p=0.002.
  • Cited CONFIRM trial in relapsed disease: overall survival was 10.2 months with nivolumab versus 6.9 months with placebo; HR 0.69 (95% CI 0.52–0.91), p=0.009.
  • Cited EMPHACIS trial: median overall survival was 12.1 months with cisplatin/pemetrexed versus 9.3 months with cisplatin alone (p=0.02).
  • Cited MARS2 trial (conference reports only, not published in full): increased mortality and reduced quality of life with neoadjuvant chemotherapy plus extended pleurectomy/decortication, with or without adjuvant chemotherapy, compared with chemotherapy alone.
  • Cited MesoVATS trial: no survival advantage for partial pleurectomy/decortication compared with talc pleurodesis (hazard ratio for death at 1 year 1.04, 95% CI 0.76–1.42, p=0.81).
  • Cited IND227 trial (440 patients): median overall survival was 17.3 months with cisplatin/pemetrexed plus pembrolizumab versus 16.1 months with cisplatin/pemetrexed; hazard ratio 0.79 (95% CI 0.64–0.98), p=0.0324.
  • Cited SMART trial: prophylactic radiotherapy did not reduce procedure-tract metastases in 203 randomised patients.
  • In Scotland, where all patients were managed and staged by a specialist multidisciplinary team, more than 50% of new cases had stage I disease.
  • The authors stated that there is no proven standard of care for early-stage disease.
  • The authors stated that second-line chemotherapy has no proven role.
• The authors' conclusion: The authors concluded that first-line ipilimumab/nivolumab has become the standard of care for most patients with later-stage, "unresectable" disease. They also concluded that the MARS2 results challenge the concept of "resectable" disease, that new trials for earlier-stage disease are urgently needed, that second-line chemotherapy has no proven role, and that specialist multidisciplinary teams should be developed further.
• Limitations the authors state:
  • The authors noted that the CheckMate743 trial recruited predominantly advanced-stage patients (89% stage III/IV), so the evidence for ipilimumab/nivolumab in stage I disease is limited.
  • The authors noted that the EMPHACIS trial recruited primarily advanced-stage patients (78% stage III/IV), so the evidence for cisplatin/pemetrexed in stage I disease is limited.
  • The authors stated that a comprehensive review of symptom control was beyond the scope of the article.
  • The authors stated that the MARS2 trial had not been published in full at the time of writing.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Median Survival, Environmental Exposure, Pemetrexed (Alimta), Chemotherapy, Second-Line Therapy, Nivolumab (Opdivo).

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