Treatment Combination Advances Metastatic Urothelial Cancer Care

Recent data has established enfortumab vedotin (EV) and pembrolizumab (P) as the preferred first-line (1L) treatment option for patients with metastatic urothelial cancer, according to an article in American Society of Clinical Oncology Educational Book.

The antibody-drug conjugate-immunotherapy combination, which was approved by the US Food and Drug Administration for all patients with locally advanced or metastatic urothelial cancer in December 2023, replaced platinum-based therapy as standard frontline treatment.

Findings from EV-302/KEYNOTE-A39 were presented at the 2023 European Society of Medical Oncology meeting. Patients with locally advanced or metastatic urothelial cancer who received EV-P had a 53% reduced risk of death compared with those who received chemotherapy consisting of cisplatin or carboplatin plus gemcitabine, according to the paper. Overall survival was 31.5 months with EV-P compared with 16.1 months with standard of care. Compared with chemotherapy, EV-P decreased the risk of progression or death by 55%.

“Certainly, it is impossible to overlook these results without optimism for the future of treatment for metastatic urothelial cancer,” wrote corresponding author Pooja Ghatalia, MD, of Fox Chase Cancer Center, Philadelphia, Pennsylvania, and coauthors.

Two noteworthy side effects of EV, however, are peripheral neuropathy and skin reactions. Peripheral neuropathy occurred in 63.2% of patients in EV-302; however, only 6.8% experienced severe grade 3 or higher.

“Thus, our ability to manage neuropathy may prove to be crucial as we begin to offer this regimen to more patients,” researchers wrote, “particularly those with diabetes who are at nascent higher risk.”

Regarding skin reactions, 46.1% of patients in a study cohort reported maculopapular rash. In 17.1%, maculopapular rash was grade 3 or higher, the paper reported.

“We are experiencing a major shift in the 1L treatment paradigm for metastatic urothelial cancer, one that is welcome with regard to its efficacy but not without concerns about tolerability and how best to limit toxicity as patients continue to live longer and receive multiple lines of therapy,” the authors wrote. “The latter is becoming the next uncharted frontier requiring dedicated, swift efforts to define the correct sequencing of therapy as platinum agents now move into the 2L and beyond setting.”

Reference
Hemenway G, Anker JF, Riviere P, Rose BS, Galsky MD, Ghatalia P. Advancements in urothelial cancer care: optimizing treatment for your patient. Am Soc Clin Oncol Educ Book. 2024;44(3):e432054. doi:10.1200/EDBK_432054