Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report

Our plain-English summary of Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report, by I. Dagogo-Jack, A. Lasko, E.A. Krueger, et al (JTO Clinical and Research Reports, 2025).

The study

• Authors: I. Dagogo-Jack, A. Lasko, E.A. Krueger, K. Tsang, R. Rao, G. Hambelton, S.R. Digumarthy
• Journal: JTO Clinical and Research Reports
• Published: 2025;6(5):100775
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Chemoimmunotherapy is associated with promising activity in mesothelioma in phase II to III trials. Studies exploring this approach in patients ineligible for clinical trials are lacking. We assembled a cohort of patients receiving pemetrexed-based chemotherapy with durvalumab outside of clinical trials.

Methods: Patients with pleural mesothelioma received pemetrexed plus durvalumab or carboplatin plus pemetrexed plus durvalumab via off-label authorization at Massachusetts General Hospital. Response to chemoimmunotherapy was assessed per modified Response Evaluation Criteria in Solid Tumors version 1.1. A retrospective chart review was conducted to assess safety per Common Terminology Criteria for Adverse Events version 5.0.

Results: Twelve patients were included in the series. Nine patients were treated with triplet chemoimmunotherapy. Three patients received doublet chemoimmunotherapy because of platinum ineligibility. Concurrent active malignancies and symptomatic cardiac disease were present in three patients (25%) and two patients (17%), respectively. Ten patients had measurable disease at baseline. With the triplet regimen, partial responses were observed in four of the seven (57%) patients with measurable disease. All three patients receiving pemetrexed plus durvalumab had measurable disease and experienced a partial response. Primary progression was not observed with either regimen. Overall, eight patients (75%) remained on treatment for more than 6 months without progression. Five patients developed immune-related adverse events (n = 1 each pyrexia, arthritis, neutropenia, Raynaud's disease, stomatitis). Three patients discontinued treatment because of toxicity or symptomatic comorbid conditions (n = 1 grade 3 heart failure, n = 1 grade 2 fever + progressive kidney cancer, n = 1 grade 2 fatigue).

Conclusions: Antitumor activity of chemoimmunotherapy reported in phase II to III clinical trials is generalizable to the broader patient population with mesothelioma. However, the tolerability of chemoimmunotherapy is impacted by comorbid conditions in real-world patients.

© 2024 The Authors.

In plain English

This was a retrospective medical record review at Massachusetts General Hospital and affiliated centers. It covered 12 patients with epithelioid pleural mesothelioma treated from February 2021 to November 2023 with durvalumab, an immunotherapy drug, plus pemetrexed-based chemotherapy outside a clinical trial. Most could not join a trial because of other cancers, heart disease, a need for reduced or no platinum chemotherapy, or limited money for travel. The article did not report asbestos exposure. Nine patients received carboplatin plus pemetrexed plus durvalumab. Tumors partly shrank in four of the seven with measurable disease. The other five of these nine, including two whose disease was not measurable at baseline, had stable disease as their best response. All three patients given pemetrexed plus durvalumab had a partial response. None had disease progression as their first response, and eight of the 12 stayed on treatment more than 6 months without progression. In the three-drug group, five patients had presumed immune-related side effects. Three of these nine stopped treatment because of side effects or other illness, despite disease control. The authors concluded that trial-ineligible patients can benefit, but that other health conditions affect tolerability.

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: Retrospective case series (medical record review) at a single institution
• Who was studied: 12 patients with pleural mesothelioma, all epithelioid type, treated off-label at Massachusetts General Hospital and affiliated satellite centers between February 2021 and November 2023. Median age was 73 (range 38 to 88). There were 8 men and 4 women, all White. They were not enrolled in the DREAM3R trial because of concurrent cancers, cardiac conditions, need for platinum dose reduction or omission, or financial constraints. Three started treatment after that trial closed. Ten were treated first-line. Two had earlier surgery and chemotherapy.
• Exposure: This was a treatment study and did not report asbestos exposure. Nine patients received carboplatin plus pemetrexed plus durvalumab. Three received pemetrexed plus durvalumab. Durvalumab was given at 1500 mg every three weeks (ten patients) or 1125 mg every three weeks (two patients).
• Main results:
  • In the carboplatin plus pemetrexed plus durvalumab group, partial responses occurred in four of seven (57%) patients with measurable disease. The best response in the remaining five of the nine patients was stable disease. Those five include the two patients with non-measurable disease.
  • All three patients receiving pemetrexed plus durvalumab had measurable disease and a partial response. The table marks one of these responses (patient 11) as unconfirmed.
  • Primary progression was not seen with either regimen. Eight of the 12 patients remained on treatment for more than 6 months without progression. The article prints this as 75%.
  • In the carboplatin plus pemetrexed plus durvalumab group, five patients (55%) had presumed immune-related adverse events: pyrexia, Raynaud's syndrome, inflammatory arthritis, stomatitis (oral lichen planus) and autoimmune neutropenia. None of the three pemetrexed plus durvalumab patients had immune-related adverse events.
  • Three of the nine carboplatin plus pemetrexed plus durvalumab patients stopped all treatment because of toxicity, despite disease control. One stopped for grade 2 pyrexia and progressive kidney cancer. One stopped for grade 3 heart failure with severe aortic stenosis. One stopped for grade 2 fatigue after 16 months.
• The authors' conclusion: The authors concluded that patients with epithelioid mesothelioma who cannot enter trials can benefit from chemoimmunotherapy. They added that tolerability is affected by comorbid conditions, so close attention to managing toxicity is needed.
• Limitations the authors state:
  • The authors listed these limitations: the series was retrospective, toxicity was not rigorously assessed, the sample was small, imaging intervals were inconsistent, only epithelioid mesothelioma was included, and the regimens varied.
  • The authors said the small number of patients does not allow them to conclude that toxicity is greater in a real-world population.

Topics

Medical terms in this study, explained in our Lexicon: Durvalumab (Imfinzi), Pemetrexed (Alimta), Chemotherapy, Mesothelioma, Clinical Trial, Pleural Mesothelioma, Carboplatin, Modified RECIST (mRECIST).

Related studies

• Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial — P.M. Forde, V. Anagnostou, et al. (2021)
• Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in — A.K. Nowak, W.J. Lesterhuis, et al. (2020)
• Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial — P.S. Kok, P.M. Forde, et al. (2022)
• Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials — G.L. Ceresoli, B. Castagneto, et al. (2008)
• Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous Cisplatin for diffuse malignant peritoneal mesothelioma — L. Bijelic, O.A. Stuart, et al. (2012)
• Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study — L. Calabrò, A. Morra, et al. (2018)

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