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

Kathryn C. Arbour, Laura Mezquita, Niamh Long, Hira Rizvi, Edouard Auclin, Andy Ni, Gala Martinez-Bernal, Roberto Ferrara, W. Victoria Lai, Lizza E. L. Hendriks, Joshua K. Sabari, Caroline Caramella, Andrew J. Plodkowski, Darragh Halpenny, Jamie E. Chaft, David Planchard, Gregory J. Riely, Benjamin Besse, Matthew D. Hellmann*

*Corresponding author for this work

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Abstract

PurposeTreatment 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.MethodsWe identified patients who were PD-(L)1-naive with advanced non-small-cell lung cancer from two institutionsMemorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Centerwho 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.ResultsNinety (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).ConclusionBaseline 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.
Original languageEnglish
Pages (from-to)2872-2878
Number of pages12
JournalJournal of Clinical Oncology
Volume36
Issue number28
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • ADVERSE EVENTS
  • DOUBLE-BLIND
  • OPEN-LABEL
  • T-CELLS
  • DYSPNEA
  • PEMBROLIZUMAB
  • DEXAMETHASONE
  • DOCETAXEL
  • FATIGUE

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