Dr Sharma on the Clinical Utility of Enfortumab Vedotin Plus Pembrolizumab in Bladder Cancer

Janaki Neela Sharma, MD, assistant professor, clinical medicine, Genitourinary Medical Oncology, University of Miami Health Systems, discusses the clinical significance of the FDA approval of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial cancer.

In December of 2023, the regulatory agency approved this combination for the treatment of patients in this populationbased on findings from the randomized, open-label, phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856). During the original presentation of the trial data, the findings received a standing ovation because of the high response rates, durable responses, and overall survival benefits, which were impressive, especially for bladder cancer, where such results are rare, Sharma begins. Initially, enfortumab vedotin plus pembrolizumab gained accelerated FDA approval for patients ineligible for cisplatin, creating a unique scenario where cisplatin-ineligible patients were eligible to receive this effective treatment but cisplatin-eligible patients were not, she states. This accelerated approval was a significant first step, offering remarkable outcomes for patients who otherwise had limited treatment options, Sharma reports.

With expanded approval now covering all patients with metastatic disease, regardless of cisplatin eligibility, enfortumab vedotin plus pembrolizumab has become a favored first-line regimen due to its manageable adverse effect profile, she continues, noting that this, however, raises questions regarding optimal sequencing for second-line treatments and beyond. Specifically, response rates with traditional chemotherapy, such as cisplatin and gemcitabine, following enfortumab vedotin plus pembrolizumab, remain unclear, Sharma emphasizes.

Sharma states that another key issue is whether the combination of enfortumab vedotin and pembrolizumab as first-line therapy is superior to the nivolumab (Opdivo) plus cisplatin and gemcitabine combination. Although preliminary data with the enfortumab vedotin and pembrolizumab combination are promising, showing better outcomes compared with nivolumab plus cisplatin and gemcitabine, there is still a need for direct, head-to-head comparisons to definitively establish superiority of one regimen over the other, Sharma says. Until such data are available, evidence-based practitioners may remain cautious, awaiting robust comparative data to confirm these findings and optimize treatment pathways for metastatic bladder cancer, she concludes.