Clinical Outcomes of Platinum-ineligible Patients with Advanced Urothelial Carcinoma Treated With First-line PD1/L1 Inhibitors

BACKGROUND: PD1/L1 inhibitors are approved by FDA as first-line therapy for patients with advanced urothelial carcinoma (aUC) who are cisplatin-ineligible with high tumor PD-L1 expression or are platinum-ineligible regardless of PD-L1 expression. However, the outcomes when employing PD1/L1 inhibitors for platinum-ineligible patients are unclear. This retrospective analysis evaluates the clinical outcomes of first-line PD1/L1 inhibitors in patients with aUC deemed to be platinum-ineligible. METHODS: Data were retrospectively collected from 8 academic institutions. The following criteria were used to define platinum ineligibility: creatinine clearance (CrCl) < 30 mL/min; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 3; CrCl 30 to 59 mL/min and ECOG PS 2; elderly and/or comorbidities. Patient characteristics, responses and treatment-related toxicities were identified. Survival curves were estimated by the Kaplan-Meier method. A Cox regression analysis was conducted to explore the association of baseline variables with response and survival. RESULTS: A total of 79 platinum-ineligible patients with aUC were eligible. Patients were treated with atezolizumab (51.9%), pembrolizumab (35.5%), nivolumab (8.9%), or durvalumab (3.8%). The objective response rate was 27.9%. The median overall survival was 45 weeks (95% confidence interval [CI], 32-80), and the median treatment failure-free survival was 16 weeks (95% CI, 9-18). Treatment-related toxicity of any grade and grade ≥ 3 was seen in 41.8% and 31.7% of patients, respectively. Anemia and liver metastasis were associated with worse survival. CONCLUSION: The efficacy of first-line PD1/L1 inhibitors for platinum-ineligible patients with aUC in the real world appears comparable to those reported in trials of unselected cisplatin-ineligible patients, whereas grade ≥ 3 toxicities appear more common. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible patients with aUC warrant evaluation of novel, safe, and effective agents.