Effectiveness and safety of first-line atezolizumab in locally advanced or metastatic urothelial cancer: The IMFLAME study.

720 Background: Urothelial cancer (UC) is the tenth most common cancer globally. Standard first-line treatment for metastatic UC (mUC) involves enfotumab-vedotin + pembrolizumab or platinum-based chemotherapies, but some patients are ineligible to standard treatment due to significant comorbidities and poor performance status. Atezolizumab, an immune checkpoint inhibitor, has shown activity in clinical trials. This study evaluates the real-world effectiveness and safety of atezolizumab as a first-line treatment in patients with locally advanced or metastatic UC ineligible for platinum-based chemotherapies. Methods: This retrospective, multicenter, observational study included 91 patients with locally advanced or mUC treated with atezolizumab monotherapy as first-line treatment in Spain. Data were extracted from medical charts, including patient demographics, clinical characteristics, treatment patterns, and outcomes. The primary endpoint was the 12-month survival rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety profile. Results: The median age at diagnosis of mUC was 77 years, and 90.1% of patients had mUC. The population had a high burden of comorbidities, 90,1% had at least 1 comorbidity, 30% of the patients had PS ECOG ≥ 2 and 42.9% had visceral metastases. The 12-month survival rate was 41.8%, decreasing to 30.8% and 19.8% at 18 and 24 months, respectively. The ORR was 45.2%, with a median DoR of 19 months (95% CI: 9.8-28.3). The median PFS was 4.1 months, and the median OS was 9.7 months. According to multivariate COX regression analysis, PS ECOG ≥ 2 was an independent prognostic factor for worse survival. Safety analysis revealed that 26.4% of patients required treatment interruption due to treatment related adverse events (TRAEs), with immune-related adverse events (irAEs) occurring in 12.1% of patients, only 6% of patients discontinued treatment due to an irAEs. Conclusions: First-line atezolizumab monotherapy provides a clinically relevant benefit in terms of response, PFS, and OS in patients with locally advanced or metastatic UC ineligible for platinum-based chemotherapies. Despite the high burden of comorbidities and poor prognosis in this population, atezolizumab demonstrated an acceptable safety profile. These findings support the use of atezolizumab in platinum-ineligible patients and potentially in those who are not suitable for EV-Pembrolizumab under routine clinical practice conditions and highlight the need for further research to optimize patient selection and management. Outcome Measure Value 95% CI 12-month survival rate (%) 41.8 33.5-55.3 18-month survival rate (%) 30.8 23.4-44.5 24-month survival rate (%) 19.8 13.6-32.5 Overall Response Rate (%) 45.2 Median PFS (months) 4.1 Median OS (months) 9.7