Improvements in Systemic Therapies for Advanced Malignant Mesothelioma

Our plain-English summary of Improvements in Systemic Therapies for Advanced Malignant Mesothelioma, by C. Deiana, F. Fabbri, S. Tavolari, et al (International Journal of Molecular Sciences, 2023).

The study

• Authors: C. Deiana, F. Fabbri, S. Tavolari, A. Palloni, G. Brandi
• Journal: International Journal of Molecular Sciences
• Published: 2023;24(13)
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies.

In plain English

This article was a narrative review of drug treatments for advanced malignant mesothelioma, mostly pleural mesothelioma. It reported no new patient data, and asbestos was mentioned only as background. The authors summarized published and ongoing trials of chemotherapy, immunotherapy, blood-vessel-blocking drugs, vaccines, and metabolism-based and targeted drugs, given first or after earlier treatment. Among results from other trials: in CheckMate 743, first-line nivolumab plus ipilimumab gave a median overall survival of 18.1 months, against 14.1 months with platinum-pemetrexed chemotherapy. In the earlier EMPHACIS trial, cisplatin plus pemetrexed gave 12.1 months, against 9.3 months with cisplatin alone. In previously treated patients, the CONFIRM trial reported 10.2 months with nivolumab and 6.9 months with placebo. The PROMISE-meso trial found no survival advantage for pembrolizumab over gemcitabine or vinorelbine. The authors concluded that the two first-line options were cisplatin-pemetrexed and nivolumab-ipilimumab. They also concluded that immunotherapy's advantage over chemotherapy was greater in non-epithelioid subtypes. In CheckMate 743, survival on immunotherapy was similar across subtypes, but survival on chemotherapy was shorter for non-epithelioid patients. They noted that the nivolumab trials in later treatment had not compared it with chemotherapy such as vinorelbine or gemcitabine.

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 and ongoing clinical trials; no new data were created or analyzed
• Who was studied: Published and registered clinical trials and other studies of systemic (drug) therapy in patients with advanced malignant mesothelioma, mostly malignant pleural mesothelioma. The studies covered first-line treatment and second or later lines of treatment and were summarized in three tables: first-line trials, second or further line trials, and ongoing trials.
• Exposure: Asbestos exposure was not studied. It was mentioned only as background, as the cause strongly associated with malignant pleural mesothelioma. The review covered drug treatments: chemotherapy, immunotherapy, antiangiogenic drugs, vaccines, metabolism-based strategies, mesothelin-targeted drugs and other targeted drugs.
• Main results:
  • As reported in the review, the CheckMate 743 phase 3 trial found a median overall survival of 18.1 months with first-line nivolumab plus ipilimumab versus 14.1 months with platinum-pemetrexed chemotherapy (hazard ratio 0.73, 95% CI 0.61 to 0.87).
  • As reported in the review, in CheckMate 743 median overall survival on immunotherapy was similar in non-epithelioid and epithelioid subtypes (18.1 vs. 18.2 months).
  • As reported in the review, in CheckMate 743 median overall survival on chemotherapy differed between non-epithelioid and epithelioid subtypes (8.8 vs. 16.7 months). The authors wrote that the trial's positive result was in part driven by the benefit of immunotherapy in non-epithelioid histology.
  • As reported in the review, the EMPHACIS phase 3 trial found a median overall survival of 12.1 months with cisplatin plus pemetrexed versus 9.3 months with cisplatin alone (p = 0.020).
  • As reported in the review, the MAPS phase 3 trial (448 untreated patients) found a median overall survival of 18.8 months with bevacizumab added to cisplatin-pemetrexed versus 16.1 months without it (p = 0.0167). Around 24.3% of patients in the bevacizumab group stopped treatment because of toxicity, compared with 6% in the standard group.
  • As reported in the review, the CONFIRM phase 3 trial (332 previously treated patients with pleural or peritoneal mesothelioma) found a progression-free survival of 3.0 versus 1.8 months and a median overall survival of 10.2 versus 6.9 months with nivolumab compared with placebo.
  • As reported in the review, the PROMISE-meso phase 3 trial of pembrolizumab versus gemcitabine or vinorelbine in previously treated patients found no advantage in progression-free survival (HR 1.06, p = 0.76) or overall survival (HR 1.04, p = 0.85).
  • As reported in the review, the RAMES phase 2 trial in patients previously treated with platinum-pemetrexed found a median overall survival of 13.8 months with gemcitabine plus ramucirumab versus 7.5 months with gemcitabine plus placebo (HR 0.71, p = 0.028).
  • As reported in the review, the VIM phase 2 trial of oral vinorelbine versus active symptom control found longer progression-free survival (4.2 vs. 2.8 months, p = 0.002) but not longer overall survival (9.3 vs. 9.1 months).
• The authors' conclusion: The authors concluded that first-line therapy for advanced mesothelioma had two viable options: the cisplatin-pemetrexed doublet and nivolumab plus ipilimumab. They wrote that CheckMate 743 pointed to better efficacy of immunotherapy, compared with chemotherapy, in non-epithelioid subtypes. For later lines, they called for large phase 3 trials comparing immunotherapy against an active treatment such as vinorelbine. They noted that none of the novel second-line approaches was in an advanced stage of testing.
• Limitations the authors state:
  • The authors noted, as a limit of the evidence they reviewed, that the nivolumab trials in second or later lines were not compared with an active option such as vinorelbine or gemcitabine, so the real-life impact is unclear.
  • The authors noted that no biomarker has been shown to correlate with response to immunotherapy, because data on PD-L1 are inconsistent.
  • The authors noted that data on vaccines combined with chemotherapy are premature, coming mostly from phase 1 trials.

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, Prognosis, Immunotherapy, PD-1/PD-L1.

Related studies

• Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements — D.C. Christoph, W.E. Eberhardt (2014)
• Combined systemic chemoimmunotherapy in advanced diffuse malignant mesothelioma. Report of a phase I-II study of weekly cisplatin/interferon alfa-2a — P. Soulié, P. Ruffié, et al. (1996)
• Local and systemic therapies for malignant pleural mesothelioma — D. Gomez, A.S. Tsao (2014)
• Real-world outcomes of first-line immunotherapy and subsequent systemic therapies in pleural mesothelioma: a multicenter study in China — B. Tian, B. Sun, et al. (2025)
• Prolonged survival with systemic chemotherapy in an advanced malignant mesothelioma: A case report — M.A. Elghali, R. Bourigua, et al. (2021)
• Chemotherapy and targeted therapies for unresectable malignant mesothelioma — R.J. Kelly, E. Sharon, et al. (2011)

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