<p>Multiple Immune-Related Adverse Events and Anti-Tumor Efficacy: Real-World Data on Various Solid Tumors</p>

TLDR

Immune checkpoint inhibitors are approved for many cancers but trigger a wide range of immune‑related adverse events, and the link between these events and clinical benefit remains unclear. The study aimed to assess, in real‑world practice, whether the occurrence of irAEs correlates with treatment efficacy in patients with metastatic non‑small‑cell lung cancer, melanoma, renal cell carcinoma, or gastric cancer receiving anti‑PD‑1/PD‑L1 therapy. A retrospective analysis of 212 patients at Keio University Hospital (2014‑2019) recorded treatment‑related adverse events graded by CTCAE v4 and performed overall survival analysis using Cox proportional hazards and shared frailty models. Patients who experienced irAEs had a significantly longer median overall survival (28.1 months vs 12.7 months, HR 0.49) and those with multiple irAEs fared even better (42.3 months vs 18.8 months, HR 0.47), indicating a favorable prognostic association.

Abstract

Immune checkpoint inhibitors (ICIs) have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in real-world practice.We conducted a retrospective study on patients with recurrent or metastatic non-small-cell lung cancer, malignant melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model and the shared frailty model.Of 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. The median OS was significantly longer in the irAEs than in the no-irAE group (28.1 months vs 12.7 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33-0.73; P = 0.0004). Moreover, the OS of patients with multiple irAEs was significantly longer than that of patients with a single irAE (42.3 months vs 18.8 months; HR, 0.473; 95% CI, 0.346-0.647; P < 0.0001).Our single-center retrospective study revealed a significant tendency associating the development of multiple irAEs with favorable prognoses.