Clinical outcomes with platinum-based chemotherapy after progression on frontline immunotherapy in metastatic urothelial cancer (mUC)

PD-1/L1 inhibitors are currently approved in the first line for patients with mUC. The outcome of patients with subsequent chemotherapy is largely unknown. An audit on patients with mUC previously treated with front-line PD-1/-L1 was performed based on data from 4 institutions (Barts Health, London, Netherland Cancer Institute, Amsterdam, Hospital 12 de Octobre, Madrid, Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas). All patients had measurable, metastatic, histology-proven disease and received at least one cycle of platinum-based chemotherapy after PD-1/-L1. Objective response rate was assessed using cross sectional imaging and was the primary endpoint. Median progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier analysis. Between Jan 2015 and Jan 2022, 51 patients were included with similar baseline characteristics. 77% (39/51) were >65 years old at the time of diagnosis of metastatic disease. 78% (40/51) received PD-1/-L1 monotherapy and 22% (11/51) had combination PD-1/CTLA-4 therapy. 20% of patients had initial response on front-line immunotherapy. After progression, 29% (15/51) and 69% (36/51) of patients received second-line gemcitabine/cisplatin and gemcitabine/carboplatin, respectively. The objective response rate was 45% (23/51). Median PFS and OS were 4.3months (95%CI: 2.7 - 6.0) and 11.9m (95%CI: 8.8 - 15.0), respectively. Platinum based chemotherapy sequenced after 1st line PD-1/L1 inhibitors for mUC is associated with significantactivity and should be considered a standard treatment option.