Abstract 139P
Background
Immune related adverse events (irAEs) due to immune checkpoint inhibitors (ICI) can lead to significant morbidity. Most clinical trials only report irAE frequency, but there is a significant need to better understand complicated irAE clinical courses. We sought to comprehensively evaluate irAE data, including timing, dynamics, and occurrence of multiple events.
Methods
The data from 2457 patients who participated in the Impower 130, 132, and 150 clinical trials investigating the PD-L1 inhibitor atezolizumab for metastatic non-small cell lung cancer were pooled for this analysis. Longitudinal irAE data with landmark analysis, changes in grading severity, and concurrent events were summarized.
Results
1557 patients were treated with atezolizumab (A) and 900 patients were in control (C) groups. Median follow up time was 32.3 months and 23.5 months for the A and C groups, respectively. In the A group, 753 patients (48.4%) experienced an irAE compared to 289 patients (32.1%) in the C group who experienced a non-immune adverse event attributed to irAE. The most common events in the A group were rash (28%), hepatitis (15%), hypothyroidism (12%), and pneumonitis (6%). 13% of these patients experienced two irAEs, most commonly rash and hepatitis (4%) followed by rash and hypothyroidism (3%), and 4% experienced three irAEs. Within five months, the cumulative incidence for all irAEs was 39.2%, but this varied between different irAEs with a lower incidence in the first five months for rash (23%), hepatitis (11%), hypothyroidism (7%), and pneumonitis (4%). IrAE grading increased in severity for some patients with grade 1 events increasing for 39% of patients, grade 2 events increasing for 21%, and grade 3 increasing for 16%. We utilized shift tables and upset plots to visually represent these complex patterns.
Conclusions
We identified differences in irAE patterns, including expected time to onset, frequency at which severity increases, and incidence of developing more than one irAE. These results can improve clinical management, represent a new standard for adverse event reporting, and inform better prospective data collection methodology to enable more comprehensive longitudinal analyses.
Clinical trial identification
NCT02367781, NCT02657434, NCT02366143.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
W. Yu: Financial Interests, Institutional, Other, Employee: Roche/Genentech. I. Bara: Financial Interests, Institutional, Full or part-time Employment: Genentech/Roche; Financial Interests, Institutional, Stocks/Shares: Genentech/Roche. G. Thanarajasingam: Non-Financial Interests, Institutional, Advisory Board: Seattle Genetics. M. Kaul: Financial Interests, Institutional, Full or part-time Employment: Genentech/Roche; Financial Interests, Institutional, Stocks/Shares: Genentech/Roche. K.A. Williams: Financial Interests, Personal, Other, Employee: Roche/Genentech. A.S. Mansfield: Financial Interests, Institutional, Research Grant: Novartis, verily; Financial Interests, Institutional, Other, grant reviewer: Rising Tide; Financial Interests, Institutional, Other, expert think tank: Triptych Health Partners; Financial Interests, Institutional, Other, steering committee: Janssen; Financial Interests, Institutional, Invited Speaker: BeiGene, Chugai Pharmaceutical (Roche); Financial Interests, Personal, Other, CME Presntation: Antoni van Leeuwenhoek Kanker Instituut; Financial Interests, Institutional, Other, CME Presentation: AXIS Medical Education, Intellisphere Llc, Answers in CME; Financial Interests, Institutional, Other, steering vommittee: Johnson & Johnson Global Services; Financial Interests, Personal, Other, CME Presentation: University of Miami Int’l Mesothelioma Symposium; Other, Personal and Institutional, Other, travel support: Roche; Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Takeda Oncology; Non-Financial Interests, Personal and Institutional, Other, non-remunerated Director: Mesothelioma Applied Research Foundation; Financial Interests, Institutional, Funding: Bristol Myers Squibb. All other authors have declared no conflicts of interest.