Abstract 3365: Preview of early adverse event landscape and association with clinical outcomes in advanced non-small cell lung cancer

Abstract Background: AE incidence and the association with clinical outcomes are still not well defined in advanced NSCLC. Most trial studies published AE results limited in treatment-related (Tr) AE using worst grade approach in descriptive manner. As a result, it fails to delineate AE landscape and explore AE potential role as a prognostic factor. Methods: All AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified by MedDRA system organ class and preferred term. The severity of AEs was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). AE data were collected from 7 advanced NSCLC trial cohorts, including 3 immunotherapy cohorts, 2 chemotherapy cohorts, and 2 targeted therapy cohorts. Early AE was defined as AE occurrence since first treatment until day 30, equivalent to period time of dose limiting toxicity. AE incidence was calculated by percentage of patients with AE experiences. Cox proportional hazards model and log-rank test were used for survival analysis. Results: Analysis of early AE landscape showed (a) low-grade AEs were more common than high-grade AEs regardless of treatment types. It makes sense otherwise the trials would be closed in early stage due to safety concern, (b) non-Tr AEs were not always more common than Tr AEs. It depends on degree of toxicity of treatments. There were one immunotherapy cohort, two chemotherapy cohorts, and one targeted therapy cohort had a higher incidence of Tr AEs over non-Tr AEs. Likely more toxic drugs were used in these cohorts, and (c) patients without non-Tr AEs may not tend to experience more low-grade Tr AEs than patients with non-Tr AEs. Two immunotherapy cohorts and one chemotherapy cohort had a higher incidence of low-grade Tr AEs in patients without versus with non-Tr AEs. In contrast, one immunotherapy cohort, one chemotherapy cohort (all patients experienced Tr AEs), and two targeted therapy cohorts had an opposite trend with higher or comparable incidence level of low-grade Tr AEs in patients with non-Tr AEs. Regarding survival association in early AEs, we found some early AE biomarkers were associated with survival outcomes in 5 cohorts. Specifically, one immunotherapy cohort and one chemotherapy cohort showed patients experienced treatment related grade 1 (Tr-G1) early overall AE had improved PFS or OS. Other significant associations were non-Tr AEs either low or high-grade level associated with poorer PFS or OS in three immunotherapy cohorts and one targeted therapy cohort. Another common pattern observed was hazard ratio (HR)>1 in high-grade AEs and HR<1 in some low-grade AEs. Conclusion: This is the first study to portray early AE outlook in advanced NSCLC. Further analysis of survival association in early AEs identified low-grade treatment related early AEs correlated with better PFS or OS. Citation Format: Dung-Tsa Chen, Jhanelle Gray, Andreas Saltos, Timothy Shaw. Preview of early adverse event landscape and association with clinical outcomes in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3365.