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© 2018 Armoiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Purpose

This systematic review with network meta-analysis compared the efficacy and safety of currently licensed second-line treatments in patients with late stage non-small cell lung cancer (NSCLC).

Methods

Randomised controlled trials (RCTs) of participants with advanced/metastatic NSCLC receiving second/third line treatments were screened. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 to July, 2017.

Two reviewers screened bibliographic records, extracted data, and assessed risk of bias of included studies. The outcomes were overall survival (OS), progression-free survival (PFS), and drug-related grade 3–5 adverse-events (AEs). We pooled study-specific hazard ratios (HR; for OS and PFS) and risk ratios (RR; for AEs) using conventional and network-meta-analyses, and ranked interventions by the surface under the cumulative ranking curve.

Findings

We included 11 RCTs (7,581 participants) comparing nine drugs. All drugs except for erlotinib significantly improved OS compared to docetaxel. Nivolumab was the highest ranking drug followed by atezolizumab and pembrolizumab. There was no significant difference in OS across these three drugs (HR = 0.98, 95% CI 0.79, 1.21 for nivolumab vs atezolizumab; HR = 0.98, 95% CI 0.77, 1.25 for nivolumab vs pembrolizumab). For PFS, ramucirumab + docetaxel and nivolumab were the drugs with the highest ranking. All interventions except ramucirumab + docetaxel had a reduced risk for severe drug-related AEs vs. docetaxel. Of the drugs with the highest ranking on AEs, nivolumab was significantly safer compared to atezolizumab (RR = 0.55, 95% CI 0.38, 0.79) or pembrolizumab (RR = 0.52, 95% CI 0.34, 0.81).

Implications

Nivolumab, pembrolizumab and atezolizumab exhibited superior benefit/risk balance compared to other licensed drugs used late stage NSCLC. Our results indicate that the use of immunotherapies in people diagnosed with non-specific late stage NSCLC should be promoted. The use of docetaxel may now be judged irrelevant as a comparator intervention for approval of new drugs for second line treatment of NSCLC.

Study registration number

PROSPERO CRD42017065928.

Details

Title
Comparative efficacy and safety of licensed treatments for previously treated non-small cell lung cancer: A systematic review and network meta-analysis
Author
Armoiry, Xavier; ⨯ Alexander Tsertsvadze; ⨯ Martin Connock; Royle, Pamela; Melendez-Torres, G J; Pierre-Jean Souquet; Clarke, Aileen
First page
e0199575
Section
Research Article
Publication year
2018
Publication date
Jul 2018
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2082087965
Copyright
© 2018 Armoiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.