Immune-Related Adverse Events and Corticosteroid Use for Cancer-Related Symptoms Are Associated With Efficacy in Patients With Non-small Cell Lung Cancer Receiving Anti-PD-(L)1 Blockade Agents

Mariona Riudavets; Joaquin Mosquera; Rosario Garcia-Campelo; Jorgina Serra; Georgia Anguera; Pablo Gallardo; Ivana Sullivan; Andrés Barba; Luís Del Carpio; Agustí Barnadas; Ignasi Gich; Margarita Majem

doi:10.3389/fonc.2020.01677

Immune-Related Adverse Events and Corticosteroid Use for Cancer-Related Symptoms Are Associated With Efficacy in Patients With Non-small Cell Lung Cancer Receiving Anti-PD-(L)1 Blockade Agents

Front Oncol. 2020 Sep 7:10:1677. doi: 10.3389/fonc.2020.01677. eCollection 2020.

Authors

Affiliations

¹ Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
² Department of Medicine, Universitat Autónoma de Barcelona (UAB), Barcelona, Spain.
³ Department of Medical Oncology, Hospital Universitario a Coruña, a Coruña, Spain.
⁴ Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁵ CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
⁶ Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain.

Abstract

Background: Immune-related adverse events (irAEs) have been associated with improved efficacy in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1 blockade agents, while the concurrent use of corticosteroids seems to worsen it. We evaluated outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents in relation to the presence of irAEs and the reasons for using corticosteroids: whether for palliative cancer-related reasons or for the management of irAEs. Methods: Clinical outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents were calculated with regard to the presence of irAEs and the use of corticosteroids. A landmark analysis was performed to avoid immortal time bias due to the time-dependent nature of irAEs. Results: Out of a total of 267 patients, the 56.9% of patients who experienced irAEs had significantly improved outcomes. In the landmark analysis, median progression-free survival (PFS) was 12.4 months for patients with irAEs vs. 4.1 months for patients without irAEs (p < 0.001), while median overall survival (OS) was 28.2 vs. 12.5 months, respectively (p < 0.001). Likewise, objective response and disease control rates were significantly higher in patients experiencing irAEs: 48.6 vs. 22.8% and 77.1 vs. 39.6% (p < 0.001), respectively. Median OS was significantly shorter for patients receiving ≥10 mg of prednisone equivalent daily for cancer-related symptoms than for the rest of patients (<10 mg prednisone equivalent daily or for management of irAEs): 6 vs. 15.9 months (p < 0.001). Conclusions: IrAEs were associated with improved efficacy in advanced NSCLC patients when a landmark analysis was applied. Patients receiving corticosteroids had significantly poorer outcomes when they were used for cancer-related symptoms.

Keywords: advanced NSCLC; corticosteroids; efficacy; immune-related adverse events; immunotherapy.