The Timing, Trajectory, and Incidence of Immune-Related Adverse Events in NSCLC Treated With Atezolizumab

Introduction: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors can have complicated clinical courses. We comprehensively evaluated the timing, trajectory, and incidence of both single and multiple irAEs for NSCLC treated with atezolizumab.Methods: Data were pooled from 2457 patients who participated in the IMpower130, IMpower132, and IMpower150 clinical trials investigating the use of atezoli-zumab in metastatic NSCLC as part of a chemo-immunotherapy regimen. Longitudinal irAE data with landmark analysis, time-to-onset, changes in grading severity, and occurrence of multiple events were summarized.Results: In general, 1557 patients were treated with ate-zolizumab and 900 patients were in the control groups. Median follow-up was 32.3 and 23.5 months, respectively. In the atezolizumab group, 753 patients (48.4%) experi-enced at least one irAE. In the control group, 289 patients (32.1%) experienced at least one nonimmune adverse event that was attributed to an irAE. In the atezolizumab group, the most common irAEs were rash, hepatitis, and hypo-thyroidism. Furthermore, 13% of the patients experienced two irAEs and 4% experienced three irAEs. Within 5 months of treatment, the cumulative incidence for any irAE was 39.2%. Median time-to-onset varied from 1 to 10 months based on the specific irAE. Grade 1 to 2 irAEs increased in severity for 33% of the patients.Conclusions: We identified dynamic clinical patterns for irAEs in patients treated with atezolizumab, including var-iations in time-to-onset, incidence of multiple irAEs, and frequency of irAEs increasing in severity. These results can guide clinical management and future reporting of adverse events to enable comprehensive longitudinal analyses.(c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).