@article{3103492,
    title = "A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial",
    author = "Popat, S. and Curioni-Fontecedro, A. and Dafni, U. and Shah, R. and O'Brien, M. and Pope, A. and Fisher, P. and Spicer, J. and Roy, A. and Gilligan, D. and Gautschi, O. and Nadal, E. and Janthur, W.D. and López Castro, R. and García Campelo, R. and Rusakiewicz, S. and Letovanec, I. and Polydoropoulou, V. and Roschitzki-Voser, H. and Ruepp, B. and Gasca-Ruchti, A. and Peters, S. and Stahel, R.A.",
    journal = "Annals of Oncology",
    year = "2020",
    volume = "31",
    number = "12",
    pages = "1734-1745",
    publisher = "Elsevier Ireland Ltd",
    issn = "0923-7534, 1569-8041",
    doi = "10.1016/j.annonc.2020.09.009",
    keywords = "antineoplastic agent;  monoclonal antibody;  pembrolizumab, clinical trial;  human;  mesothelioma;  multicenter study;  phase 3 clinical trial;  tumor recurrence, Antibodies, Monoclonal, Humanized;  Antineoplastic Combined Chemotherapy Protocols;  Humans;  Mesothelioma, Malignant;  Neoplasm Recurrence, Local",
    abstract = "Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. Patients and methods: PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0–1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. Results: Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9–14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73–1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1–4.2), compared with 3.4 (2.2–4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8–19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74–1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. Conclusion: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy. © 2020 European Society for Medical Oncology"
}