Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer

Abstract

Background: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. Methods: A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. Results: 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (p p = 0.014 and HR0.41 [95% CI 0.26–0.63], p p p p = 0.011), but not on 24-week landmark analyses (p = 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (p = 0.015). Conclusion: The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value.

Keywords

• biomarkers of systemic inflammation
• Scottish Inflammatory Prognostic Score (SIPS)
• non-small-cell lung cancer
• immune-related adverse events
• pembrolizumab