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

Katherine E R Smith; Stephanie L Pritzl; Wei Yu; Ilze Bara; Gita Thanarajasingam; Monika D Kaul; Kirstin A Williams; Amylou C Dueck; Aaron S Mansfield

doi:10.1016/j.jtocrr.2023.100611

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

JTO Clin Res Rep. 2023 Nov 23;4(12):100611. doi: 10.1016/j.jtocrr.2023.100611. eCollection 2023 Dec.

Authors

Katherine E R Smith¹, Stephanie L Pritzl¹, Wei Yu², Ilze Bara², Gita Thanarajasingam³, Monika D Kaul², Kirstin A Williams², Amylou C Dueck⁴, Aaron S Mansfield¹

Affiliations

¹ Department of Oncology, Mayo Clinic, Rochester, Minnesota.
² Genentech Inc., South San Francisco, California.
³ Department of Hematology, Mayo Clinic, Rochester, Minnesota.
⁴ Department of Quantitative Health Sciences, Mayo Clinic, Phoenix, Arizona.

Abstract

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 atezolizumab in metastatic NSCLC as part of a chemoimmunotherapy 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 atezolizumab 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%) experienced 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 hypothyroidism. 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 variations 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.

Keywords: Atezolizumab; Immune checkpoint inhibitors; Immune-related adverse events; Non–small cell lung cancer.