@article{b2a87cfff93b4937b4fbb16c986d0418,
title = "Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression",
abstract = "Background: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. Patients and methods: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes. Results: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. Conclusion: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.",
keywords = "NSCLC, PD-L1, pembrolizumab",
author = "Aguilar, {E. J.} and B. Ricciuti and Gainor, {J. F.} and Kehl, {K. L.} and S. Kravets and S. Dahlberg and M. Nishino and Sholl, {L. M.} and A. Adeni and S. Subegdjo and S. Khosrowjerdi and Peterson, {R. M.} and S. Digumarthy and C. Liu and J. Sauter and H. Rizvi and Arbour, {K. C.} and Carter, {B. W.} and Heymach, {J. V.} and M. Altan and Hellmann, {M. D.} and Awad, {M. M.}",
note = "Funding Information: MMA is a consultant in Merck, Bristol-Myers Squibb, Genetech, AstraZeneca, Nektar, Ariad. Research Funding: Bristol-Myers Squibb. LMS performs consulting for LOXO Oncology, Foghorn Therapeutics; received honorarium from AstraZeneca; received travel grant from Bristol Myers Squibb; and received research support from Roche. MA received research funding from Bristol Myers Squibb and Lilly. JS: Pfizer, Merck, Thermo Fisher Scientific. JFG is a consultant or received honoraria from Bristol-Myers Squibb, Genentech/Roche, Ariad/ Takeda, Loxo, Pfizer, Incyte, Novartis, Merck, Agios, Amgen, Regeneron, Oncorus, Array, Jounce and Clovis Oncology; received research support from Novartis, Genentech/Roche, and Ariad/Takeda; and received institutional research support from Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, Novartis, and Alexo. SD performs consulting for AstraZeneca. JVH has participated in scientific advisory boards for Genentech, BMS, Lilly, AstraZeneca, Merck, Boehringer, GSK, Spectrum; received research support from AstraZeneca, Spectrum; and received royalties from licensing from Spectrum. MN is a consultant to Toshiba Medical Systems, WorldCare Clinical, Daiichi Sankyo; and received research grant from Merck, Canon Medical Systems, AstraZeneca; Honorarium from Bayer and Roche. SD provided independent image analysis through hospital for clinical research trial program sponsored by Merck, Pfizer, Bristol Mayer Squibb, Novartis, Roche, Polaris, Cascadian, Abbvie, Gradalis, Clinical Bay, Zai laboratories; and received honorarium from Siemens Medical Services. KA is a consultant or received honoraria from AstraZeneca and The Jackson Laboratory. MDH received research funding from Bristol-Myers Squibb. Consultant to Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Janssen, Nektar, Syndax, Mirati, and Shattuck Labs; received travel support/honoraria from AztraZeneca and BMS. A patent has been filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. All remaining authors have declared no conflicts of interest. Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2019",
month = oct,
day = "1",
doi = "10.1093/annonc/mdz288",
language = "English (US)",
volume = "30",
pages = "1653--1659",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "10",
}