التفاصيل البيبلوغرافية
العنوان:
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
المؤلفون:
Popat, S. Curioni-Fontecedro, A. Dafni, U. Shah, R. O'Brien, M. Pope, A. Fisher, P. Spicer, J. Roy, A. Gilligan, D. Gautschi, O. Nadal, E. Janthur, W.D. López Castro, R. García Campelo, R. Rusakiewicz, S. Letovanec, I. Polydoropoulou, V. Roschitzki-Voser, H. Ruepp, B. Gasca-Ruchti, A. Peters, S. Stahel, R.A.
سنة النشر:
2020
الوصف:
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
اللغة:
English
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=od______2127::9d89bd27aadaf498f31dbfebbb2829b5 https://pergamos.lib.uoa.gr/uoa/dl/object/uoadl:3103492
حقوق:
OPEN
رقم الأكسشن:
edsair.od......2127..9d89bd27aadaf498f31dbfebbb2829b5
قاعدة البيانات:
OpenAIRE
