Real-world effectiveness and safety of avelumab first-line maintenance (1LM) treatment in patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Second interim analysis of the AVENUE study.

706 Background: Avelumab 1LM is standard of care for patients with la/mUC without disease progression after 1L platinum-based chemotherapy (PBC) based on results from the JAVELIN Bladder 100 phase 3 trial. The AVENUE study is evaluating the effectiveness and safety of avelumab 1LM treatment in routine clinical practice in Germany, Spain, Switzerland, and Russia. Previous results showed the acceptable safety profile of avelumab 1LM in a heterogeneous real-world population. Here, we report initial effectiveness data and updated baseline and safety data from the second interim analysis. Methods: AVENUE is a prospective, noninterventional study in patients with la/mUC without disease progression after 1L PBC. Initiation of avelumab 1LM is decided by the treating physician prior to enrollment per local approval. Patients are followed for 36 mo. The primary objective is to evaluate the overall survival (OS) rate at 12, 24, and 36 mo. Secondary objectives include assessment of median OS, progression-free survival (PFS), tumor response, and safety. Results: By data cutoff (May 9, 2024), 177 patients had received avelumab 1LM (median follow-up, 10.0 mo). Median age was 70 years (range, 43-89) and 78% were male. ECOG PS was 0-1 in 89.3%, ≥2 in 5.1%, and not reported (NR) in 5.6%. Primary tumor site was upper or lower tract in 28.2% and 71.8%, respectively. 1L PBC regimen was gemcitabine + cisplatin in 61.0% (split dose in 8.5%), gemcitabine + carboplatin in 36.2%, and other/switch in 3.4%. Number of prior PBC cycles was <4, 4-6, >6, and NR in 12.4%, 84.2%, 2.8%, and 0.6%, respectively. Median time to avelumab 1LM initiation was 6.1 weeks (range, 0.3-80.4) and median treatment duration was 6.0 mo (range, 0.5-30.8). Median OS was not reached (95% CI, 17.0-not estimable) and 6- and 12-mo OS rates (95% CI) were 80.6% (73.9-85.7) and 69.1% (61.1-75.7), respectively. Median PFS was 5.8 mo (95% CI, 4.6-9.1) and 6- and 12-mo PFS rates (95% CI) were 50.0% (42.1-57.3) and 33.1% (25.2-41.2). Disease control rate (assessed up to 6 mo) was 66.9% (95% CI, 58.8-74.3). Treatment-related adverse events (TRAEs) occurred in 57.6%, were grade ≥3 in 15.8%, serious in 15.3%, and led to permanent discontinuation in 10.7%. The most common TRAEs of any grade (≥4.0%) were fatigue (9.6%), hyperthyroidism (5.1%), pruritus (4.5%), and diarrhea (4.0%). Grade ≥3 immune-related AEs and infusion-related reactions occurred in 6.2% and 3.4%, respectively. At last follow-up, 28.8% of patients remained on avelumab, and 34.5% and 8.5% had received second- or third-line treatment (enfortumab vedotin in 21.5% and 2.3%), respectively. Conclusions: Data from the second interim analysis of AVENUE confirm the effectiveness and acceptable safety profile of avelumab 1LM in patients with la/mUC treated in routine clinical practice, consistent with previous studies.