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. 2023 Nov 21;15(23):5502.
doi: 10.3390/cancers15235502.

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

George Raynes  1 , Mark Stares  1   2 , Samantha Low  1 , Dhania Haron  1 , Hussain Sarwar  1 , Dhruv Abhi  1 , Colin Barrie  1 , Barry Laird  2 , Caledonian Cachexia Collaborative, Iain Phillips  1   2 , Melanie MacKean  1
Affiliations

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

George Raynes et al. Cancers (Basel). .

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 <= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41-0.90], p = 0.014 and HR0.41 [95% CI 0.26-0.63], p < 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34-1.90], p < 0.001) and OS (HR 1.69 [95% CI 1.41-2.02], p < 0.001). SIPS predicted the occurrence of any irAE in all patients (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: Scottish Inflammatory Prognostic Score (SIPS); biomarkers of systemic inflammation; immune-related adverse events; non-small-cell lung cancer; pembrolizumab.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier survival curves examining the relationship between the occurrence of immune-related adverse events and progression-free survival or overall survival in (A) all patients, and (B) 12-week landmark and (C) 24-week landmark cohorts. n/r = not reached.
See this image and copyright information in PMC

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