678 Background: Avelumab 1LM is the standard of care for patients (pts) with la/mUC without progression after 1L platinum-based chemotherapy. We assessed the long-term effectiveness and safety of avelumab 1LM based on real-world evidence (RWE). Methods: An SLR of all observational studies published in any language between 1/1/2020 and 7/11/2025 was conducted in MEDLINE, Embase, and Cochrane. Data were narratively synthesized. Landmark 12- and 24-mo progression-free survival (PFS) and overall survival (OS) rates measured from avelumab 1LM start were pooled for MA. Results: The SLR included 83 unique studies comprising >7,000 pts treated with avelumab 1LM; 65 studies (78%) were retrospective. Most studies (n=56; 67%) were based in the US and Europe. RW pts receiving avelumab 1LM were generally older than JAVELIN Bladder 100 (JB100) pts, with median age of ≥70 in 77% (36/47) of studies. Pts with an ECOG performance score of 0-1 ranged from 66-100%. Overall, 4-54% of pts had upper tract UC. The rates of liver (4-19%) and lung metastases (14-42%) in RWE were similar to those in JB100. Between 21% and 100% of pts with disease progression received second-line therapy after avelumab 1LM, of whom 24-88% (17% and 10% in 1 study each) received enfortumab vedotin. Median OS (95% CI) from avelumab 1LM start ranged from 10.6 (3.4-15.5) to 39.5 mo (13.2-65.7). In the MA, 12- and 24-mo OS rates (95% CI) from avelumab 1LM start were 74% (69-78) and 55% (46-63). Median PFS (95% CI) from avelumab 1LM start ranged from 3.3 (2.0-4.7) to 11.5 mo (6.9-16.1). In the MA, 12- and 24-mo PFS rates (95% CI) from avelumab 1LM start were 39% (36-43) and 26% (22-30). Discontinuation rates due to adverse events (AEs) and grade ≥3 AE rates were 1-21% and 0-38% (50% in 1 study), respectively (Table). Conclusions: Our review provides a comprehensive quantitative overview of RWE, which demonstrates the beneficial effect of avelumab 1LM in routine care settings, consistent with findings from JB100. No new safety concerns were observed with long-term avelumab use. These findings offer further reassurance to healthcare providers of the established role of avelumab 1LM as part of the JAVELIN Bladder regimen in optimizing treatment decisions and sequencing for pts with la/mUC. Clinical and safety outcomes with avelumab 1LM. Outcome median across studies Outcome IQR across studies JB100 (ITT; median FU, 38 mo) Avelumab duration, median, mo 5.7 4.1-7.0 5.8 (range 0.5-49.7) Median PFS, mo* 6.2 5.6-8.9 5.5 (95% CI 4.2-7.2) 12 mo PFS, % 40.8 33.6-44.9 34 24 mo PFS, % 27.2 25.3-29.5 23.4 Median OS, mo* 21.6 17.4-23.4 23.8 (95% CI 19.9-28.8) 12 mo OS, % 75.2 67-78 72 24 mo OS, % 53.2 47.7-66.8 49.8 Grade ≥3 AEs, % 6.9 5.1-15.0 54 Discontinuation due to AEs, % 9.5 7.2-13.1 14 FU, follow-up; IQR, interquartile range; ITT, intention to treat. *From avelumab 1LM start.
Barthelemy et al. (2026) studied this question.