Dr. Galsky on Maintenance Pembrolizumab in Urothelial Cancer

Matthew Galsky, MD, director, Genitourinary Medical Oncology, The Tisch Cancer Institute, Mount Sinai Hospital, discusses the HCRN GU14-182 study, which looked at maintenance pembrolizumab (Keytruda) versus placebo after first-line chemotherapy in patients with metastatic urothelial cancer.

The current standard of treatment for patients with metastatic urothelial cancer is platinum-based chemotherapy, generally given for 6 to 8 cycles then discontinued due to concerns of increasing toxicity with diminishing benefit, according to Galsky. Most patients with urothelial cancer regress within a short period of time on first-line chemotherapy. Therefore, due to those situations, studies have started to explore the switch maintenance approach in metastatic urothelial cancer. The switch maintenance method is given upon the discontinuation of first-line chemotherapy.

Initial chemotherapy could potentially induce immunogenic cell death or cause depletion of immunosuppressive cellular subsets, thereby enhancing the effects of subsequent immune checkpoint blockade, Galsky explained. Additionally, chemotherapy and immune checkpoint blockade are non-cross resistant in this disease. One-third of patients who start first-line chemotherapy for metastatic urothelial cancer are able to go onto subsequent lines of treatment, according to Galsky. By moving treatment earlier in the course of the disease, patients may benefit by ensuring that they gain access or exposure to potentially active, non-cross resistant treatments.

The study, of which Galsky is the lead author, is a randomized, double-blind, phase II study. Patients with metastatic urothelial cancer received up to 8 cycles of first-line platinum-based chemotherapy and then were randomized 1:1 to receive pembrolizumab versus placebo. Treatment continued for up to 24 months in the absence of disease progression. Results showed that there was significant improvement in progression-free survival with switch maintenance pembrolizumab compared with placebo.