New Therapies Set Stage for Dramatic Changes in Bladder Cancer

Matthew Galsky, MD
Published: Monday, Nov 18, 2019
Matthew Galsky, MD

Matthew Galsky, MD
The vast majority of patients with urothelial cancer of the bladder present with non–muscleinvasive disease, and a large proportion can be effectively managed with transurethral resections with or without intravesical medication. However, once the disease invades the bladder’s muscle layer, the risk of metastatic dissemination increases, prompting a need for more intensive treatment.

and other genes involved in DNA damage response and repair have been associated with high rates of pathological complete response with neoadjuvant cisplatin-based chemotherapy. These alterations are being tested as predictors of response to systemic chemotherapy in patients with muscle-invasive disease. The goal is to discover whether systemic treatment might be curative in this group and dispel the need for cystectomy.

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Mutations in FGFR3, present in 10% to 15% of muscle-invasive urothelial cancers, were recently shown to confer sensitivity to treatment with small molecule FGFR3 inhibitors in patients with platinumresistant metastatic disease. The FDA approved the first targeted systemic therapy for the treatment of urothelial cancer, erdafitinib (Balversa), in April 2019.

Immune checkpoint blockade has dramatically changed the treatment landscape for urothelial cancer. Some of the first presurgical trials tested ipilimumab (Yervoy) in patients with urothelial cancer and demonstrated proof-of-concept pharmacodynamic effects, including infiltration of T cells in posttreatment cystectomy specimens. After demonstrating activity in advanced solid tumors not typically thought to be sensitive to immunotherapy such as lung cancer, PD-1/ PD-L1 inhibitors became the focus of clinical investigation. This work led to the approval of 5 agents for the treatment of platinum-resistant metastatic disease between 2016 and 2017: atezolizumab (Tecentriq), nivolumab (Opdivo), durvalumab (Imfinzi), avelumab (Bavencio), and pembrolizumab (Keytruda).

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