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

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...

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Main Authors: Ibiayi Dagogo-Jack, MD, Aubrey Lasko, PharmD, Elizabeth A. Krueger, NP, Kitman Tsang, NP, Revati Rao, MD, Grace Hambelton, BA, Subba R. Digumarthy, MD
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:JTO Clinical and Research Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666364324001450
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author Ibiayi Dagogo-Jack, MD
Aubrey Lasko, PharmD
Elizabeth A. Krueger, NP
Kitman Tsang, NP
Revati Rao, MD
Grace Hambelton, BA
Subba R. Digumarthy, MD
author_facet Ibiayi Dagogo-Jack, MD
Aubrey Lasko, PharmD
Elizabeth A. Krueger, NP
Kitman Tsang, NP
Revati Rao, MD
Grace Hambelton, BA
Subba R. Digumarthy, MD
author_sort Ibiayi Dagogo-Jack, MD
collection DOAJ
description 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.
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spelling doaj-art-2bbba20ba98f452fa442ea14060069c92025-08-20T01:49:12ZengElsevierJTO Clinical and Research Reports2666-36432025-05-016510077510.1016/j.jtocrr.2024.100775Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief ReportIbiayi Dagogo-Jack, MD0Aubrey Lasko, PharmD1Elizabeth A. Krueger, NP2Kitman Tsang, NP3Revati Rao, MD4Grace Hambelton, BA5Subba R. Digumarthy, MD6Massachusetts General Hospital Cancer Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Corresponding author. Address for correspondence: Ibiayi Dagogo-Jack, MD, Department of Medicine, Massachusetts General Hospital, 32 Fruit Street, Yawkey 7B, Boston, Massachusetts 02114.Massachusetts General Hospital Cancer Center, Boston, MassachusettsMassachusetts General Hospital Cancer Center, Boston, MassachusettsMassachusetts General Hospital Cancer Center, Boston, MassachusettsHarvard Medical School, Boston, Massachusetts; Department of Medicine, Newton Wellesley Hospital, Newton, MassachusettsMassachusetts General Hospital Cancer Center, Boston, MassachusettsHarvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2666364324001450MesotheliomaChemoimmunotherapyImmunotherapyDurvalumab
spellingShingle Ibiayi Dagogo-Jack, MD
Aubrey Lasko, PharmD
Elizabeth A. Krueger, NP
Kitman Tsang, NP
Revati Rao, MD
Grace Hambelton, BA
Subba R. Digumarthy, MD
Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report
JTO Clinical and Research Reports
Mesothelioma
Chemoimmunotherapy
Immunotherapy
Durvalumab
title Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report
title_full Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report
title_fullStr Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report
title_full_unstemmed Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report
title_short Durvalumab Combined With Pemetrexed-Based Chemotherapy in Trial-Ineligible Patients With Mesothelioma: A Brief Report
title_sort durvalumab combined with pemetrexed based chemotherapy in trial ineligible patients with mesothelioma a brief report
topic Mesothelioma
Chemoimmunotherapy
Immunotherapy
Durvalumab
url http://www.sciencedirect.com/science/article/pii/S2666364324001450
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