Abstract 1749P
Background
Immune checkpoint inhibitors (ICIs) are an integral part in the treatment of mUC. In some cancer types, studies have shown an association between the development of ICI-associated imAEs and outcomes. In this exploratory post hoc analysis of the phase 3 DANUBE study, we evaluated the association between imAEs and outcomes in patients (pts) with mUC treated with D (1500 mg Q4W) or D+T (1500 mg D+75 mg T Q4W, up to 4 doses, followed by D Q4W).
Methods
Patient-level data for D and D+T were analyzed, including age, sex, Eastern Cooperative Oncology Group performance status, and programmed death ligand-1 expression (tumor cells ≥25% or immune cells ≥25% algorithm). Treatment, imAEs, and outcomes (overall survival [OS], progression-free survival [PFS]) were collected. Cox modeling was performed, with imAEs as a time-varying covariate, while estimating median OS (mOS) and hazard ratios (HR) in pts with and without imAEs.
Results
A total of 346 pts received D and 342 pts received D+T. For D, 63/346 (18.2%) pts developed an imAE: Grade 1/2 (n=40), Grade ≥3 (n=23). For D+T, 126/342 (36.8%) pts developed an imAE: Grade 1/2 (n=67), Grade ≥3 (n=59). The most common imAEs were endocrine (D, n=23; D+T, n=45), skin (D, n=11; D+T, n=20), and GI-related (D, n=8; D+T, n=35). For D and D+T combined, pts who developed an imAE had higher mOS (447 days, 95% CI [307–768]) than pts who did not (mOS: 422 days, 95% CI [368–460]; HR 0.80, 95% CI [0.65–0.98], P=0.03). For D+T, pts with an imAE had a higher mOS than pts without (506 days, 95% CI [324–893] vs 428 days, 95% CI [370–546]; HR 0.73, P=0.02). The association was less clear for D alone. Overall and within treatment arms, analyses of PFS did not show a significant association with imAEs.
Conclusions
In mUC, this analysis is one of the first to examine the association between imAEs and OS. Exploratory data from DANUBE showed that patients who developed an imAE on treatment with D+T had a longer mOS than those not developing an imAE. Impact of imAEs on mUC outcomes warrants further exploration and appropriate imAE management remains critical for patients to continue ICI treatment and derive optimal therapeutic benefit.
Clinical trial identification
NCT02516241.
Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Lauren D. Van Wassenhove, PhD of Parexel (Hackensack, NJ) and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
C. Lu: Financial Interests, Stocks/Shares: AstraZeneca; Financial Interests, Full or part-time Employment: AstraZeneca. H. Zhang: Financial Interests, Full or part-time Employment: AstraZeneca; Financial Interests, Stocks/Shares: AstraZeneca. E.T. Goluboff: Financial Interests, Stocks/Shares: AstraZeneca; Financial Interests, Full or part-time Employment: AstraZeneca. S. Sridhar: Financial Interests, Research Grant: Bayer, Janssen; Financial Interests, Invited Speaker: Roche, Merck, Pfizer, AstraZeneca, BMS, Janssen, Bayer, Astellas, Sanofi Aventis, Immunomedex. All other authors have declared no conflicts of interest.