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

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.

Figure 1

Landmark analysis according to the presence of irAEs. (A) Progression-free survival and the presence of irAEs (n = 175). (B) Overall survival and the presence of irAEs (n = 167). Kaplan-Meier curves with 2.4 months landmark analysis for progression-free survival (A) and 5.9 months for overall survival (B) in patients with or without irAEs. Abbreviations: PFS, progression-free survival; OS, overall survival; irAEs, immune-related adverse events; CI, confidence interval; HR, hazard ratio; m, months.

Figure 2

Survival analysis with regard to corticosteroid use (≥10 mg of prednisone equivalent daily). (A) Overall survival and the use of ≥10 mg of prednisone equivalent daily (n = 267). (B) Overall survival and the reason for corticosteroid use (n = 267). (C) Overall survival and corticosteroid use (n = 267). Abbreviations: PFS, progression-free survival; OS, overall survival; irAEs, immune-related adverse events; PDNe, prednisone equivalent; CI, confidence interval; HR, hazard ratio; m, months. Kaplan-Meier curves of patients treated with anti-PD-(L)1 blockade agents on the basis of reported corticosteroid usage (≥10 mg of prednisone equivalent) in terms of OS (A). OS comparison in patients who did not received any corticosteroids, those who received them for irAEs treatment or cancer-related symptoms management (B). OS comparison according to the use of corticosteroids: for management of cancer-related symptoms and the rest of the population (C). ^aUse of ≥10 mg of prednisone equivalent daily for irAEs management. ^bUse of ≥10 mg of prednisone equivalent daily for cancer-related symptoms.