Dr Gopal on Treatment Selection in Second-Line R/R mUC

Nikhil A. Gopal, MD, assistant professor, urology, assistant professor, College of Medicine - Memphis, Department of Urology, The University of Tennessee Health Science Center, discusses treatment selection in the second line and beyond for patients with relapsed/refractory metastatic urothelial cancer.

In recent years, the treatment arsenal for relapsed/refractory metastatic urothelial cancer has expanded significantly with the approval of novel agents targeting specific molecular alterations, Gopal begins. Antibody-drug conjugates (ADCs) such as enfortumab-ejfv vedotin (Padcev) and sacituzumab govitecan-hziy (Trodelvy) have demonstrated significant efficacy in the second line, as have targeted therapies such as erdafitinib (Balversa), he states.

Navigating treatment selection for patients with relapsed/refractory disease in the second line and beyond should therefore involve a selective precision medicine strategy, driven by molecular and genetic profiling of the tumor, Gopal states. He explains that this profiling helps guide treatment decisions based on specific mutations and biomarkers present in the tumor.

For instance, the presence of FGFR3 mutations in a patient's tumor may make them a candidate for erdafitinib, Gopal says. There is also interest in utilizing anti-HER2 agents such as trastuzumab (Herceptin) for tumors expressing HER2 mutations, he adds. Furthermore, evaluating tumor mutational burden or microsatellite instability (MSI) status can inform the use of immunotherapy regimens, which may be more effective in tumors with high mutational burden or MSI-high status, Gopal explains.

It is also crucial to consider the toxicity profiles of available treatments alongside molecular findings, Gopal continues. Although enfortumab vedotin is a highly effective regimen, a patient with neuropathy may experience more significant adverse effects (AEs). Conversely, erdafitinib is associated with ocular toxicities, making it less appropriate for patients with pre-existing eye disorders, Gopal states.

This underscores the importance of utilizing precision medicine to tailor therapy to each patient's unique tumor characteristics, optimizing treatment efficacy while minimizing the risk of AEs, Gopal emphasizes. Moving forward, the integration of comprehensive molecular profiling into routine clinical practice will continue to guide therapeutic decision-making in this challenging disease setting, he concludes.