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Association between Early Immune-Related Adverse Events and Survival in Patients Treated with PD-1/PD-L1 Inhibitors
You-Cheng Zhang1,2, Tian-Chen Zhu1,2, Run-Cong Nie1
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Background:
Immune-related adverse events (irAEs) are side effects that reflect the activation of patients' immune systems after treatment with immune checkpoint inhibitors (ICIs). However, there is no meta-analysis on the effect of early irAEs on patient survival. Thus, we assessed the association between early irAEs and the survival of patients treated with ICIs.
Methods:
PubMed, Embase, and Web of Science were searched from May 2010 to May 2020 for all the retrospective and prospective comparative studies to evaluate the hazard ratios (HRs) for death. A random-effects model was used to calculate the pooled HR for death, and heterogeneity was assessed using I² statistics. The main outcomes were overall survival (OS) and progression-free survival (PFS).
Results:
A total of 11 reports with 2077 patients were included. A significant association was observed between early irAEs and a favorable clinical outcome. Patients with early irAEs had prolonged OS (HR: 0.62, 95% confidence interval (CI): 0.53-0.74, p < 0.001) and PFS (HR: 0.53, 95% CI: 0.41-0.66, p < 0.001) compared to those without; these results were confirmed using a sensitivity analysis. The irAE types, malignancy types, and sample size were correlated with patients' clinical outcomes.
Conclusions:
Early irAEs, especially cutaneous irAEs, correlated with a better clinical outcome in patients treated with ICIs.
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