Baseline Steroids and Efficacy of PD-1/PD-L1 Inhibitors in NSCLC
In a study reported in the Journal of Clinical Oncology, Arbour et al found that baseline treatment with corticosteroids was associated with poorer efficacy of programmed cell death protein 1 (PD-1) or programmed death cell ligand 1 (PD-L1) inhibitors in patients with non–small cell lung cancer (NSCLC). As stated by the investigators, “On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy [of these agents], but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown.”
Study Details
Clinical trials of PD-1/PD-L1 inhibitors generally have excluded patients receiving baseline corticosteroids. Thus, the study examined the effect of baseline corticosteroids in PD-1/PD-L1 inhibitor–naive patients starting single-agent therapy in the ‘real-world’ setting at Memorial Sloan Kettering Cancer Center (MSKCC; n = 455) and Gustave Roussy Cancer Center (GRCC; n = 185).
Association With Outcomes
Overall, 90 (14%) of 640 patients treated with single-agent PD-1/PD-L1 blockade received corticosteroids of ≥ 10 mg of prednisone equivalent daily at the start of treatment, including 53 (12%) of the MSKCC cohort and 37 (20%) of the GRCC cohort. Indications for steroid treatment included dyspnea (33%), fatigue (21%), and brain metastases (19%).
In the MSKCC cohort, use of baseline corticosteroids of ≥ 10 mg was associated with decreased overall response rate (6% vs 19%, P = .02), shorter median progression-free survival (1.9 vs 2.6 months, hazard ratio [HR] = 1.7, P = .001), and shorter median overall survival (5.4 months vs 12.1 months, HR = 2.1, P < .001). In the GRCC cohort, such use was associated with a nonsignificantly lower overall response rate (8% vs 18%, P = .2), reduced median progression-free survival (1.7 vs 1.8 months, HR = 1.5, P < .001), and reduced median overall survival (3.3 vs 9.4 months, HR = 2.0, P < .001). In multivariate analysis of the pooled population adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroid use remained significantly associated with decreased progression-free survival (HR = 1.3, P = .03) and overall survival (HR = 1.7, P < .001).
The investigators concluded, “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-1/PD-L1] blockade. Prudent use of corticosteroids at the time of initiating [PD-1/PD-L1] blockade is recommended.”
Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
