Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies.


Journal

Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225

Informations de publication

Date de publication:
11 2019
Historique:
received: 06 02 2019
revised: 05 04 2019
accepted: 10 06 2019
pubmed: 4 8 2019
medline: 26 3 2020
entrez: 4 8 2019
Statut: ppublish

Résumé

Extended onset of treatment effect and longer-term survival with anti-programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non-small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources. Studies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival. PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%). This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.

Sections du résumé

BACKGROUND
Extended onset of treatment effect and longer-term survival with anti-programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non-small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources.
MATERIALS AND METHODS
Studies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival.
RESULTS
PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%).
CONCLUSION
This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.

Identifiants

pubmed: 31375454
pii: S1525-7304(19)30159-7
doi: 10.1016/j.cllc.2019.06.017
pii:
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
B7-H1 Antigen 0
Cd274 protein, mouse 0
PDCD1 protein, human 0
Programmed Cell Death 1 Receptor 0

Types de publication

Comparative Study Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

451-460.e5

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Christian Schulz (C)

University Hospital Regensburg, Regensburg, Germany. Electronic address: christian.schulz@klinik.uni-regensburg.de.

David Gandara (D)

University of California Davis Comprehensive Cancer Center, Sacramento, CA.

Carmen G Berardo (CG)

F. Hoffman-La Roche Ltd, Basel, Switzerland.

Rachel Rosenthal (R)

F. Hoffman-La Roche Ltd, Basel, Switzerland.

Jason Foo (J)

Mapi Group (an ICON plc Company), Houten, the Netherlands.

Chaienna Morel (C)

Mapi Group (an ICON plc Company), Houten, the Netherlands.

Marcus Ballinger (M)

Genentech, Inc, South San Francisco, CA.

Claire Watkins (C)

Clarostat Consulting Ltd, Alderly Edge, Cheshire, UK.

Paula Chu (P)

F. Hoffman-La Roche Ltd, Basel, Switzerland.

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