Dr Park on Navigating of Later-line Treatment Options in Metastatic Urothelial Carcinoma

Chandler Park, MD, MSc, FACP, co-director, Genitourinary Clinical Trials, Norton Cancer Institute, discusses the navigation and selection of later-line treatments for patients with metastatic urothelial carcinoma.

The number of available therapeutic options in bladder cancer has significantly expanded in recent years, Park begins. There is also a substantial amount of new data on the use of molecular testing and circulating tumor DNA for patients with stage II disease, he adds. However, precision medicine approaches are needed to navigate later-line treatment decisions for patients in the metastatic setting who have progressed on platinum-doublet chemotherapy in combination with avelumab (Bavencio), Park says. 

Tools like next-generation sequencing could be used to identify patients whose tumors harbor FGFR2 or FGFR3 alterations, Park explains. These patients may benefit from a targeted therapy such as erdafitinib (Balversa). 

Conversely, the antibody-drug conjugate (ADC) enfortumab vedotin-ejfv (Padcev) is an effective option for patients who do not harbor these mutations, Park continues. In April 2023, this agent was granted accelerated approval in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible based on data from cohort A and cohort K of the phase 1/2 EV-103/KEYNOTE-869 study (NCT03288545). Enfortumab vedotin is also approved in the United States for patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

Additionally, other ADCs like sacituzumab govitecan-hziy (Trodelvy) my serve as an effective alternative to enfortumab vedotin for patients who have aggressive peripheral neuropathy, according to Park. This adverse effect is commonly observed in those receiving cisplatin and gemcitabine-based regimens, and is also seen in almost half of patients treated with enfortumab vedotin, Park adds. Accordingly, enfortumab vedotin is not an option for this population, he concludes.