Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma

Abstract

Background: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab.

Materials and methods: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety.

Results: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death.

Conclusion: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

Keywords: durvalumab; immune checkpoint inhibitors; malignant pleural mesothelioma; second line.

Conflict of interest statement

Disclosure PAZ declares payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events and for the participation on a Data Safety Monitoring Board or Advisory Board from Merck Sharp and Dohme, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer; FG declares payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Astra Zeneca and Eli Lilly; ER, FG, IDS, and LC declare that funding was given to Istituto di Ricerche Farmacologiche Mario Negri IRCCS to partially support the study; DLC declares payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events and for the participation on a Data Safety Monitoring Board or Advisory Board from BMS, MSD, Astra Zeneca, Boehringer Ingelheim, Lilly, Amgen, Roche, and Novartis. All other authors have declared no conflicts of interest.

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Survival curves. Progression-free survival (A) and overall survival (B). Kaplan–Meier curve—all enrolled patients. CI, confidence interval; NE, not estimable.

Supplementary Fig S1

Study flowchart – All enrolled patients.

Supplementary Fig S2

Progression free survival (A) and overall survival (B) according to the PD-L1 expression. Kaplan-Meier curve – All enrolled patients.