A combination therapy, new option for patients with advanced urothelial cancer who cannot receive conventional chemotherapy

Patients with locally advanced or metastatic urothelial cancer who are unable to receive cisplatin chemotherapy, which is the conventional first-line treatment for this disease, face very limited options to combat their condition. Unfortunately, this is not an exceptional situation, as renal insufficiency, for example, is among the factors that contraindicate this therapeutic alternative when dealing with a tumor that affects the urinary system.

Now, a study in which Dr. José Pablo Maroto, a researcher from the Clinical Oncology Group at the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and an oncologist at the same hospital, has participated, has been able to verify that the combination of two drugs, enfortumab vedotin and pembrolizumab, which had previously shown benefits in survival in second-line treatment and in cases of advanced urothelial cancer, offers results comparable to cisplatin chemotherapy.

It is a Phase II study, called EV-103, which analyzes data from a specific cohort of patients with locally advanced or metastatic urothelial cancer who were not suitable to receive cisplatin. The results are published in the Journal of Clinical Oncology, with Dr. Maroto as the sole Spanish author.

The main conclusion of the study is that patients who received this new therapeutic combination – enfortumab vedotin and pembrolizumab – showed a high response rate, and the effects were long-lasting, which positions it as a good option for first-line treatment. These results represent a significant advancement in the treatment of advanced urothelial cancer and offer new hope for patients facing this disease who cannot undergo cisplatin chemotherapy.

Until now, patients with advanced or metastatic urothelial cancer who could not receive cisplatin chemotherapy, either due to renal insufficiency, peripheral neuropathy, hearing problems, cardiac issues, or poor overall condition, were given a carboplatin-derived drug that offered much inferior results. “Cisplatin is a drug that is eliminated through the renal route and therefore requires patients to be well-hydrated. In the case of frail patients or those with renal problems, we cannot prescribe it, and thus, we cannot offer the optimal treatment,” comments Dr. Maroto.

Currently, the confirmatory Phase III clinical trial is underway. If its results are positive as expected, they would lay the groundwork for the approval of this therapeutic combination in Spain, which is currently under investigation.

Reference article

O’Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N, Moon HH, Friedlander TW, McKay RR, Bilen MA, Srinivas S, Burgess EF, Ramamurthy C, George S, Geynisman DM, Bracarda S, Borchiellini D, Geoffrois L, Maroto Rey JP, Ferrario C, Carret AS, Yu Y, Guseva M, Homet Moreno B, Rosenberg JE. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023 Jun 27:JCO2202887. doi: 1200/JCO.22.02887. Epub ahead of print. PMID: 37369081.