Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression Journal Article

Authors: Aguilar, E. J.; Ricciuti, B.; Gainor, J. F.; Kehl, K. L.; Kravets, S.; Dahlberg, S.; Nishino, M.; Sholl, L. M.; Adeni, A.; Subegdjo, S.; Khosrowjerdi, S.; Peterson, R. M.; Digumarthy, S.; Liu, C.; Sauter, J.; Rizvi, H.; Arbour, K. C.; Carter, B. W.; Heymach, J. V.; Altan, M.; Hellmann, M. D.; Awad, M. M.
Article 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. © 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.
Keywords: nsclc; pd-l1; pembrolizumab
Journal Title: Annals of Oncology
Volume: 30
Issue: 10
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2019-10-01
Start Page: 1653
End Page: 1659
Language: English
DOI: 10.1093/annonc/mdz288
PUBMED: 31435660
PROVIDER: scopus
Notes: Source: Scopus
Citation Impact
MSK Authors
  1. Corinne Liu
    5 Liu
  2. Matthew David Hellmann
    259 Hellmann
  3. Kathryn Cecilia Arbour
    35 Arbour
  4. Hira Abbas Rizvi
    48 Rizvi
  5. Jennifer Lynn Sauter
    54 Sauter