Leveraging Early-Onset Adverse Events (aes) to Inform Treatment Strategies in Pan-Gastrointestinal (GI) Cancer.

842 Background: Few studies have evaluated the role of early-onset adverse events (AEs) on treatment outcomes for patients with GI cancer. This study aims to develop a pan-GI cancer AE profile to facilitate modernization of treatment strategies. Methods: We evaluated 10 study cohorts from Moffitt Cancer Center: 3 in biliary (n=115), 2 in colorectal (n=89), 2 in pancreatic r (n=44), 1 in gastric (n=23), 1 in hepatocellular (n=14), and 1 in pan GI cancers (n=16), for a total of 301 patients. Treatment included 1 cohort with immunotherapy (IO), 2 with targeted therapy (TT), 2 with combination of TT and IO, and 5 with chemotherapy (Chemo)+TT. Data for analysis used CTCAE version 4 AE data, treatment response, progression-free survival (PFS), and overall survival (OS). Our analytic approach leveraged multiple AE parameters to develop a set of innovative AE biomarkers. Early-onset AEs were defined as events that occurred between the first day and day 30 after the first treatment. Results: In the 10 aggregated GI cohorts (n=301), patients experiencing with higher frequency of grade 1 (G1) early-onset treatment related (Tr) AEs tended to improve PFS and OS (p<0.05). Other TrAEs also showed a non-significant trend toward hazard ratio (HR) <1, suggesting a potential but inconclusive benefit for PFS and OS. In contrast, all non-TrAEs had a HR>1, indicating poor survival with significant associations for grade 2 (G2) and grade > 2 (G>2) in OS. Similar findings were observed across the 9 pooled TT cohorts (n=247). For the 3 merged IO cohorts (n=143), patients presenting G1 early-onset TrAEs exhibited improved OS compared to those without AEs (p=0.02). Most grade 1-2 (G1/2) TrAEs showed HR<1 in PFS and OS. Conversely, all non-TrAEs had HR>1 with significance achieved in G2 and higher grade for OS. The 5 combined chemo cohorts (n=107) showed a nonsignificant HR <1 in PFS and OS for most G1/2 TrAEs; conversely, all non-TrAEs were associated with HR>1 with significant effects in G2 or higher grade for OS. Conclusions: This study presents compelling evidence supporting the clinical relevance of early-onset AEs in predicting pan-GI cancer patient outcomes. Specifically, G1 and G1/2 early-onset TrAEs showed robust results as potential indicators of improved OS or PFS in the entire combined cohorts and in the subset analysis for TT and IO. Even the cohorts with Chemo had a nonsignificant HR<1. Timely recognition of treatment response or disease progression is essential for optimizing clinical decision-making. The pan-GI cancer early-onset AEs may serve this function, supporting more precise treatment strategies and improved patient outcomes.