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
Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 31(2020), 12 vom: 01. Dez., Seite 1734-1745 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Popat, S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.01.2021 Date Revised 06.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.annonc.2020.09.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315476974 |
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| 041 | |a eng | ||
| 100 | 1 | |a Popat, S |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma |b the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.01.2021 | ||
| 500 | |a Date Revised 06.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a immune-checkpoint inhibition | |
| 650 | 4 | |a malignant pleural mesothelioma | |
| 650 | 4 | |a pembrolizumab | |
| 650 | 4 | |a randomised clinical trial | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a pembrolizumab |2 NLM | |
| 650 | 7 | |a DPT0O3T46P |2 NLM | |
| 700 | 1 | |a Curioni-Fontecedro, A |e verfasserin |4 aut | |
| 700 | 1 | |a Dafni, U |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, R |e verfasserin |4 aut | |
| 700 | 1 | |a O'Brien, M |e verfasserin |4 aut | |
| 700 | 1 | |a Pope, A |e verfasserin |4 aut | |
| 700 | 1 | |a Fisher, P |e verfasserin |4 aut | |
| 700 | 1 | |a Spicer, J |e verfasserin |4 aut | |
| 700 | 1 | |a Roy, A |e verfasserin |4 aut | |
| 700 | 1 | |a Gilligan, D |e verfasserin |4 aut | |
| 700 | 1 | |a Gautschi, O |e verfasserin |4 aut | |
| 700 | 1 | |a Nadal, E |e verfasserin |4 aut | |
| 700 | 1 | |a Janthur, W D |e verfasserin |4 aut | |
| 700 | 1 | |a López Castro, R |e verfasserin |4 aut | |
| 700 | 1 | |a García Campelo, R |e verfasserin |4 aut | |
| 700 | 1 | |a Rusakiewicz, S |e verfasserin |4 aut | |
| 700 | 1 | |a Letovanec, I |e verfasserin |4 aut | |
| 700 | 1 | |a Polydoropoulou, V |e verfasserin |4 aut | |
| 700 | 1 | |a Roschitzki-Voser, H |e verfasserin |4 aut | |
| 700 | 1 | |a Ruepp, B |e verfasserin |4 aut | |
| 700 | 1 | |a Gasca-Ruchti, A |e verfasserin |4 aut | |
| 700 | 1 | |a Peters, S |e verfasserin |4 aut | |
| 700 | 1 | |a Stahel, R A |e verfasserin |4 aut | |
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