Avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) with or without diabetes mellitus (DM): Long-term outcomes from JAVELIN Bladder 100.

869 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1LM + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (PBC). In some cancers, the presence of DM has been associated with reduced efficacy of immunotherapy; however, data in UC are limited. We report post hoc exploratory analyses from JAVELIN Bladder 100 in pts with or without DM at randomization. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 1L PBC were randomized 1:1 to receive avelumab + BSC or BSC alone. The primary endpoint was OS measured from randomization; secondary endpoints included PFS measured from randomization and safety. Results: At randomization in the avelumab + BSC (n=350) and BSC alone (n=350) arms, 55 (15.7%) and 59 (16.9%) pts had documented controlled DM, and 295 and 291 pts did not have documented DM, respectively. Median follow-up in both arms was ≥38.0 months (data cutoff, June 4, 2021). In pts with or without DM, OS and PFS (investigator assessed) were prolonged with avelumab + BSC vs BSC alone (Table). In the safety analysis set of avelumab-treated pts with (n=54) or without (n=290) DM, respectively, treatment-related adverse events (AEs) of any grade occurred in 75.9% and 78.6% (grade ≥3 in 24.1% and 18.6%) and led to avelumab discontinuation in 9.3% and 12.1%; immune-related AEs of any grade occurred in 31.5% and 32.4%. Limitations include the exploratory nature of the analysis and the potential for missing DM diagnosis. Conclusions: In exploratory analyses, avelumab 1LM was associated with long-term efficacy and consistent safety in pts with aUC with or without DM. Clinical trial information: NCT02603432 . Pts with DM Pts without DM Avelumab + BSC (n=55) BSC alone (n=59) Avelumab + BSC (n=295) BSC alone (n=291) Median OS (95% CI), months 20.8 (18.0-32.4) 14.5 (11.7-21.3) 24.7 (19.9-30.0) 15.8 (13.3-18.7) 2-year OS (95% CI), % 44.5 (30.7-57.3) 34.1 (22.2-46.3) 50.7 (44.8-56.4) 39.4 (33.6-45.2) 3-year OS (95% CI), % 33.1 (20.4-46.4) 20.3 (10.8-31.9) 36.6 (30.6-42.6) 31.9 (26.3-37.7) Hazard ratio (95% CI) 0.60 (0.37-0.95) 0.78 (0.64-0.96) Median PFS (95% CI), months 5.6 (3.7-9.3) 2.0 (1.9-3.7) 5.4 (3.8-7.2) 2.1 (1.9-3.5) 2-year PFS (95% CI), % 18.5 (9.1-30.6) 9.2 (3.4-18.6) 24.3 (19.3-29.7) 6.5 (3.8-10.2) 3-year PFS (95% CI), % 13.5 (5.5-25.1) 5.5 (1.4-13.8) 16.3 (11.7-21.6) 5.3 (2.9-8.9) Hazard ratio (95% CI) 0.50 (0.33-0.77) 0.54 (0.45-0.65)