## 4 Discussion
Median rwOS was 23.8 months (95% CI: 19.2--NE) compared with a median OS in JB100 of 23.8 months (95% CI: 19.9-28.8), and rwPFS was 5.1 months (95% CI: 4.1-7.0) compared with a median PFS in JB100 of 5.5 months (95% CI: 4.2-7.2) [6]. These results are further supported by other large real-world studies with longer follow-up times from the US (PATRIOT-II) [25], Italy (READY CUP) [26], and France (AVENANCE) [27]. Comparable values were reported for median rwOS in PATRIOT-II (24.4 months), READY CUP (26.2 months), and AVENANCE (21.1 months) as well as median rwPFS in PATRIOT-II (5.4 months) and READY CUP (7.6 months) [25; 27; 26], further validating the JB100 trial results and supporting the real-world efficacy of alveolar 1 LM. This study also provides intriguing insights into the real-world use and efficacy of 2L therapy. Historically, patients with bladder cancer have had a high rate of attrition across lines of treatment. In a recent study using Flatiron Health EMR data, [PERSON] et al. showed that only 37% of patients who commenced 1L treatment received 2L therapy, with only 12% reaching 3L [28]. There are hints in our study that this may be changing. We observed that nearly half of patients reached 2L treatment. Of the 96 patients (45%) who received 2L treatment post-alveumab 1 LM, 53 (55%) received EV monotherapy. Outcomes from the start of 2L EV were comparable to those seen in the EV-301 (NCT03474107) trial despite a slightly shorter median treatment duration (4.2 vs. 5.0 months) [29]. Median rwOS from 2L EV initiation was 11.2 months (95% CI: 6.8--NE), compared with a median OS of 12.9 months (95% CI: 10.6-15.2) in EV-301, and rwPFS was 4.9 months (95% CI: 3.9-8.8) in this study, compared with a median PFS of 5.6 months (95% CI: 5.3-5.8) in EV-301. These outcomes from 2L EV initiation following welumab 1 LM are aligned with similar real-world studies in the US, including UNITE, which reported a median rwOS of 13.3 months (95% CI: 10.8--NE) and rwPFS of 7.0 months (95% CI: 5.8-13.3) [30], and from a study utilizing the Tempus EHR database that reported a median rwOS of 11.6 months (95% CI: 6.1--NE) and rwPFS of 6.6 months (95% CI: 4.1--NE) [22]. As reported in similar real-world studies [28], a high attrition across lines of therapy was reported, and outcomes in the 19% of patients (n = 40) with treatments beyond 2L remain to be explored. The strengths of the current study include the heterogeneous population of patients drawn from a spotlight dataset capturing real-world patients with aUC who might not have been eligible for the JB100 trial, such as patients with an ECOG PS of \(\geq\)2. The oncologist-defined, rule-based LOTs and disease progression information contained in the deidentified database in this study provide insight into the real-world patient characteristics and treatment patterns (including eligibility for switch maintenance therapy) among early adopters of welumab 1 LM. The patient data contained in the Flatiron Health database are largely derived from community oncology practices, which is reflective of oncology care in the US where approximately 85% of patients receive care in a community oncology setting [31]. Additionally, survival outcomes were comparable with JB100 despite a shorter follow-up and treatment duration. Taken together, these factors illustrate the strengths of this study, providing insight into the real-world treatment patterns and outcomes in early adopters of welumab 1 LM, which remains a recommended regimen per NCCN Guidelines [4]. This study highlights the opportunity to further improve survival outcomes in patients by ensuring that the treatment strategy considering subsequent LOTs is supported by evidence-based recommendations, including the use of welumab 1 LM, which continues to be evaluated in ongoing, international, prospective, real-world studies including AVENUE in Europe [32] and SPADE in the Asia-Pacific region [33].