OBJECTIVES: Avelumab 1LM is widely recommended by guidelines for patients with la/mUC who did not progress after 1L platinum-based chemotherapy (PBC) based on the JAVELIN Bladder 100 trial. While trial data remains the gold standard for evaluating therapies, real-world evidence (RWE) provides insights for the clinical practice in a broader population. We aimed to evaluate the effectiveness and tolerability of avelumab 1LM from the most recent RWE studies.

METHODS: An SLR was conducted for observational studies in MEDLINE, Embase, and Cochrane (01/01/2020-31/01/2024), with no language restrictions. Landmark 1-year progression-free survival (PFS) and 1-year overall survival (OS), measured from avelumab 1LM start, were included in MA.

RESULTS: Overall, 45 studies were identified, encompassing 2656 patients treated with avelumab 1LM, most often from the US (15/45), EU5 (14/45), and Japan (5/45). Across studies, patients’ mean age was 71 years and majority were male (78%) and had an ECOG performance score (PS) of 0-1 (81%). On average, 26%, 14%, and 25% had upper tract tumors, liver, and lung metastases, respectively. More than half of patients received second-line (2L) treatment (55%) after avelumab 1LM. The most common 2L therapy was enfortumab vedotin (36% of patients). Median OS from avelumab start varied between 10.6 (range 3.4-15.5) to 26.2 months (95%CI 19.97-not estimable). In the MA, 1-year PFS and OS rates (95% CI) from avelumab 1LM start were 39% (35%-44%) and 69% (65%-73%), respectively. Rates of grade ≥3 adverse events (AEs) and discontinuation due to AEs were low (median 8% and 9% across studies, respectively).

CONCLUSIONS: The effectiveness and safety of avelumab 1LM was consistent with those seen in JAVELIN Bladder 100, despite data heterogeneity and limited follow-up. Global RWE supports the established clinical benefit seen with avelumab 1LM in a broad range of patients, such as older pts and those with high metastatic tumor burden or ECOG PS>1.