Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non–small-cell lung cancer Journal Article

Authors: Arbour, K. C.; Mezquita, L.; Long, N.; Rizvi, H.; Auclin, E.; Ni, A.; Martínez-Bernal, G.; Ferrara, R.; Lai, W. V.; Hendriks, L. E. L.; Sabari, J. K.; Caramella, C.; Plodkowski, A. J.; Halpenny, D.; Chaft, J. E.; Planchard, D.; Riely, G. J.; Besse, B.; Hellmann, M. D.
Article Title: Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non–small-cell lung cancer
Abstract: Purpose Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation. Methods We identified patients who were PD-(L)1–naïve with advanced non–small-cell lung cancer from two institutions—Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center—who were treated with single-agent PD-(L)1 blockade. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti–PD-(L)1 therapy. We performed multivariable analyses using Cox proportional hazards regression model and logistic regression. Results Ninety (14%) of 640 patients treated with single-agent PD-(L)1 blockade received corticosteroids of $ 10 mg of prednisone equivalent daily at the start of the PD-(L)1 blockade. Common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%). In both independent cohorts, Memorial Sloan Kettering Cancer Center (n = 455) and Gustave Roussy Cancer Center (n = 185), baseline corticosteroids were associated with decreased overall response rate, progression-free survival, and overall survival with PD-(L)1 blockade. In a multivariable analysis of the pooled population, adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroids remained significantly associated with decreased progression-free survival (hazard ratio, 1.3; P = .03), and overall survival (hazard ratio, 1.7; P, .001). Conclusion Baseline corticosteroid use of $ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non–small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended. Copyright © 2018 American Society of Clinical Oncology. All rights reserved.
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 28
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-10-01
Start Page: 2872
End Page: 2878
Language: English
DOI: 10.1200/jco.2018.79.0006
PROVIDER: scopus
PUBMED: 30125216
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
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MSK Authors
  1. Jamie Erin Chaft
    120 Chaft
  2. Gregory J Riely
    334 Riely
  3. Matthew David Hellmann
    147 Hellmann
  4. Ai   Ni
    45 Ni
  5. Joshua K Sabari
    20 Sabari
  6. Niamh   Long
    11 Long
  7. Kathryn Cecilia Arbour
    13 Arbour
  8. Hira Abbas Rizvi
    18 Rizvi
  9. Wei-Chu Victoria Lai
    10 Lai