Clinical outcomes of platinum-ineligible patients with advanced urothelial carcinoma treated with first-line pd1/l1 inhibitors

Abstract Background PD1/L1 inhibitors are approved 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) 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 overall response rate (ORR) was 27.9%. The median overall survival was 45 weeks (95% 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 aUC patients in the real world appears comparable to those reported in trials of unselected cisplatin-ineligible patients, while 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.