# Checkpoint inhibitor effectiveness after corticosteroids and second-line immunosuppressants for immune-related adverse events in non-small-cell lung cancer

## TL;DR

High-dose corticosteroids used to treat immune-related adverse events in lung cancer patients receiving immunotherapy may reduce survival rates.

## Contribution

This study is the first large-scale analysis showing that high peak corticosteroid doses impair survival in non-small-cell lung cancer patients treated with immunotherapy.

## Key findings

- Higher peak corticosteroid doses were linked to worse overall and cancer-specific survival in stage IV NSCLC patients.
- Cumulative corticosteroid dose and second-line immunosuppressants did not affect survival outcomes.
- The study highlights the need to balance rapid adverse event management with potential survival risks from high-dose steroids.

## Abstract

Recent studies have demonstrated that high-dose corticosteroids and second-line immunosuppressants may impair survival of patients with immune-related adverse events (irAEs) upon treatment with immune checkpoint inhibitors (ICIs). In non-small-cell lung cancer (NSCLC), this has not been studied in sufficiently powered studies. This study assessed the association of corticosteroid dose and second-line immunosuppressants for irAEs with survival outcomes in patients with stage IV NSCLC treated with ICIs.

Patients with stage IV NSCLC treated with ICI-based regimens between 2015 and 2022 in the first or second line who received systemic immunosuppressants for irAEs were retrospectively included from 17 hospitals in eight countries worldwide. Associations of corticosteroid peak and cumulative dose, and use of second-line immunosuppressants with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression.

Of 419 included patients, 339 (80.9%) were treated with corticosteroids only and 80 (19.1%) received second-line immunosuppressants. Higher corticosteroid peak dose was associated with impaired OS [adjusted hazard ratio (HRadj) 1.63, 95% confidence interval (CI) 1.27-2.08 for an increase by 80 mg prednisolone equivalent] and CSS (HRadj 1.54, 95% CI 1.13-2.08), but not PFS (HRadj 1.05, 95% CI 0.75-1.48). The cumulative corticosteroid dose and use of second-line immunosuppressants were not associated with survival.

Treatment with high corticosteroid peak dose for irAEs is associated with impaired survival in patients with stage IV NSCLC receiving ICI. Treatment of severe irAEs often requires high doses of corticosteroids. However, clinicians should weigh the unfavorable effects of high peak doses against the need for rapid irAE management.

•Previous studies suggest that immunosuppressive treatment of irAEs impairs survival in patients treated with ICI.•The effect of immunosuppression for irAEs on survival has not been studied in large NSCLC populations.•In this study, treatment with high steroid peak doses for irAEs was associated with impaired OS and CSS in stage IV NSCLC.•The cumulative steroid dose and use of second-line immunosuppression were not associated with impaired survival.•This suggests considerate steroid use when treating irAEs, weighing benefits against potential detrimental survival effects.

Previous studies suggest that immunosuppressive treatment of irAEs impairs survival in patients treated with ICI.

The effect of immunosuppression for irAEs on survival has not been studied in large NSCLC populations.

In this study, treatment with high steroid peak doses for irAEs was associated with impaired OS and CSS in stage IV NSCLC.

The cumulative steroid dose and use of second-line immunosuppression were not associated with impaired survival.

This suggests considerate steroid use when treating irAEs, weighing benefits against potential detrimental survival effects.