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

“EV-302 read out [in 2023]... [Data from this study] led to the eventual full FDA approval of [treatment with enfortumab vedotin plus pembrolizumab] in patients with bladder cancer in the frontline [setting].”

Janaki Neela Sharma, MD, assistant professor, clinical medicine, Genitourinary Medical Oncology, University of Miami Health Systems, discusses how data from the randomized, open-label, phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) further defined the role of frontline enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in patients with advanced urothelial cancer, irrespective of cisplatin eligibility.

This study included a broad population of patients with previously untreated metastatic bladder cancer, comparing the combination therapy against the standard chemotherapy regimen of gemcitabine and cisplatin, Sharma begins. The findings from EV-302 ultimately supported the FDA’s full approval of enfortumab vedotin plus pembrolizumab for the first-line treatment of patients with locally advanced or metastatic urothelial cancer in December 2023, she reports.

The EV-302 trial demonstrated a significant overall survival (OS) benefit with the use of the combination therapy, Sharma continues. The median OS was 31.5 months (95% CI, 25.4-not reached) for patients treated with enfortumab vedotin plus pembrolizumab compared with 16.1 months (95% CI, 13.9-18.3) for patients who received standard-of-care chemotherapy (HR, 0.47; 95% CI, 0.38-0.58;P < .001), she states. Importantly, the OS advantage was consistent across cisplatin-eligible and cisplatin-ineligible patients, as highlighted by a preplanned subgroup analysis, Sharma notes, adding that this uniform survival benefit underscores the broad applicability of the combination therapy, regardless of a patient’s ability to tolerate cisplatin.

The overall response rate (ORR) data further emphasized the effectiveness of enfortumab vedotin plus pembrolizumab, Sharma expands. Patients who received the combination achieved a confirmed ORR of 67.7% (95% CI, 63.1%-72.1%),significantly surpassing the 44.4% (95% CI, 39.7%-49.2%) ORR observed with standard chemotherapy, she says. These robust response rates, coupled with improved survival outcomes, establish enfortumab vedotin plus pembrolizumab as a highly effective frontline treatment option for patients with advanced urothelial cancer, offering new hope for improved treatment outcomes across diverse patient populations, Sharma concludes.