Sequential Endoluminal Gemcitabine and Cabazitaxel with Intravenous Pembrolizumab as a Bladder-Preserving Strategy for Docetaxel-Unresponsive Non-Muscle Invasive Urothelial Carcinoma Following Transurethral Resection of Bladder Tumor

Simple Summary After failing the first-line treatment of high-risk non-muscle invasive urothelial carcinoma (NMIUC), salvage intravesical therapies are important to preserve patient quality of life and avoid radical surgery. However, some patients will develop a disease resistant to commonly used drug regimens. We aimed to evaluate a novel combinatory therapy consisting of intravesical sequential gemcitabine and cabazitaxel with concomitant systemic pembrolizumab (GCP) for patients with recurrent high-risk NMIUC of the bladder and upper urinary tracts. We found in a population of 26 patients with 31 treated units (bladder and/or upper urinary tracts) that, following GCP treatment, over half of the treated units remained disease-free at 2 years. In this highly pretreated population, the progression of disease was a concern with an estimated 30% rate of progression at 2 years. However, only 4% of the population experienced cancer-related death during this same time. Lastly, this regimen was well tolerated, with all patients completing the scheduled induction course.Abstract Growing evidence suggests that many patients with high-risk non-muscle invasive urothelial carcinoma (NMIUC) can undergo bladder-sparing management with salvage intravesical therapies. However, inherent or developed disease resistance, particularly after multiple lines of prior salvage therapy, implores the continued pursuit of new treatment combinations. Herein, we describe the outcomes of 26 patients (31 treated units; 24 lower tract, 7 upper tract) with high-risk NMIUC treated with sequential intravesical gemcitabine and cabazitaxel with concomitant intravenous pembrolizumab (GCP) at the University of Iowa from August 2020 to February 2023. Median (IQR) follow-up was 30 (IQR: 17-35) months. Treated units had a history of high-risk NMIUC with a median of four prior endoluminal inductions. Overall, 87% of units presented with CIS or positive urine cytology. The 1- and 2-year recurrence-free survival was 77% (CI: 58-88%) and 52% (CI: 30-70%), respectively. The 2-year progression-free and cancer-specific survival was 70% (CI: 44-85%) and 96% (CI: 75-99%), respectively. In total, 22/26 (85%) patients reported any adverse event and 5/26 (19%) reported a grade >= 3 adverse event; however, all patients tolerated a full induction course. These results suggest that GCP is an effective and tolerable treatment option for patients with recurrent high-risk NMIUC.