Management and outcomes of rash, peripheral neuropathy (PN), and hyperglycemia (HG) during first-line (1L) treatment (tx) of locally advanced/metastatic urothelial cancer (la/mUC) in a real-world setting.

Abstract

e23275 Background: Real-world data on adverse events (AEs) among contemporary 1L Tx regimens for la/mUC are limited. Rash, PN, and HG are potential dose-limiting toxicities associated with several 1L Tx regimens for la/mUC. This study aims to characterize the management and outcomes of rash, PN, and HG in a real-world setting. Methods: This retrospective observational cohort study used the nationwide US Flatiron Health electronic health record–derived deidentified database and included adults diagnosed with la/mUC who initiated 1L Tx with a regimen of interest after Jan 1, 2016. Machine learning (ML) was used to extract clinician documentation of rash, PN, and HG from 1L Tx initiation to the earliest of: 90 days after last 1L Tx dose, start of subsequent Tx, or death. A manual chart review was conducted for a subset of patient records with ML-extracted evidence of rash, PN, or HG to assess: hospitalizations and deaths attributable to the AEs, 1L Tx modification due to the AEs (dose holds, dose changes, dose schedule changes, and discontinuations), and any Tx received for the AE. All analyses were conducted among the overall sample and stratified by 1L Tx group (Table). Results: Of 5235 patients (pts) who met study criteria, 938 (18%) experienced rash, 228 (4%) experienced PN, and 175 (3%) experienced HG. Manual chart review of a subset of pts with rash (n=164), PN (n=132), and HG (n=73) revealed that hospitalization due to the AE was relatively rare, but highest for HG (n=8; 11%); no deaths were attributed to any of the AEs examined. Regarding management, a similar proportion of the overall pts who experienced rash, PN, and HG required 1L Tx modification due to the AE (Table). When stratified by Tx group, 1L Tx modifications due to these 3 AEs occurred most frequently in pts who received enfortumab vedotin + pembrolizumab (EV+P) for all AEs examined. The proportion of pts requiring 1L Tx modification was lowest in the platinum-based chemotherapy (PBC) with avelumab 1L maintenance (1LM) group for rash and in the immune checkpoint inhibitor (ICI) monotherapy group for PN and HG. Tx for the AE was required in 84%, 43%, and 71% of rash, PN, and HG cases, respectively. Conclusions: Management and outcomes of AEs vary across 1L Tx regimens for la/mUC in real-world settings. Understanding the outcomes, Tx interventions, and impact of AEs on a pts’ ability to receive sustained 1L therapy is crucial for evaluating the safety profiles of different regimens and can inform clinical decision making. No. (%) of pts with any 1L Tx modification by AE and 1L Tx group. AE Overall EV+P ICI monotherapy PBC without avelumab 1LM PBC with avelumab 1LM Rash 39/164 (23.8) 16/50 (32.0) 11/43 (25.6) 7/36 (19.4) 5/35 (14.3) PN 31/132 (23.5) 20/35 (57.1) 1/24 (4.2) 5/34 (14.7) 5/39 (12.8) HG 14/73 (19.2) 5/17 (29.4) 2/20 (10.0) 4/22 (18.2) 3/14 (21.4)