TY - JOUR
TI - 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
AU - Popat, S.
AU - Curioni-Fontecedro, A.
AU - Dafni, U.
AU - Shah, R.
AU - O'Brien, M.
AU - Pope, A.
AU - Fisher, P.
AU - Spicer, J.
AU - Roy, A.
AU - Gilligan, D.
AU - Gautschi, O.
AU - Nadal, E.
AU - Janthur, W.D.
AU - López Castro, R.
AU - García Campelo, R.
AU - Rusakiewicz, S.
AU - Letovanec, I.
AU - Polydoropoulou, V.
AU - Roschitzki-Voser, H.
AU - Ruepp, B.
AU - Gasca-Ruchti, A.
AU - Peters, S.
AU - Stahel, R.A.
JO - Annals of Oncology
PY - 2020
VL - 31
TODO - 12
SP - 1734-1745
PB - Elsevier Ireland Ltd
SN - 0923-7534, 1569-8041
TODO - 10.1016/j.annonc.2020.09.009
TODO - 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
TODO - 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
ER -