Correlation between irAEs and survival outcomes in patients with ES-SCLC treated with first-line chemoimmunotherapy

Abstract

Introduction: Chemo-immunotherapy (CT-IO) has improved median overall survival (mOS) for patients with extensive-stage small cell lung cancer (ES-SCLC), but its association with immune-related adverse events (irAEs) remains unclear. While irAEs are often linked to better outcomes in other cancers, their prognostic value in ES-SCLC is not well understood.

Methods: We conducted a retrospective analysis of 399 consecutive ES-SCLC patients treated with first-line CT-IO between January 2020 and September 2024 across five European centres. Demographic and clinical data were collected. The impact of irAEs on progression-free survival (PFS) and overall survival (OS) was assessed using time-dependent Cox regression.

Results: The median follow-up was 15.0 months. The overall response rate was 80.3 %, with a median PFS of 6.0 months (95 % CI 5.7-6.3) and mOS of 10.4 months (95 % CI 9.2-11.6). IrAEs occurred in 30.6 % of patients, most commonly affecting the skin (11.0 %). The median time to onset of irAEs was 171 days. Patients with irAEs had significantly longer mPFS (10.8 vs. 5.3 months, p < 0.001) and mOS (18.8 vs. 7.6 months, p < 0.001) compared to those without. No significant difference was found between patients with grade ≥ 3 (n = 46) and < 3 irAEs (n = 76). Multivariate analysis confirmed that irAEs were associated with improved OS (HR 0.64; 95 % CI 0.51-0.80, p < 0.001) and showed a trend towards longer PFS (p = 0.028).

Conclusion: This is the largest retrospective study to demonstrate that irAEs are associated with improved clinical outcomes in ES-SCLC pts receiving 1 L CT-IO.

Keywords: Corticosteroid use; Cutaneous Toxicity; Endocrine toxicity; Extensive Stage; High-grade immune-related adverse events; Immune check point inhibitors; Immune-related Adverse Events; Immunotherapy; Small Cell Lung Cancer.