Dr Sharma on Key Trials Within the Urothelial Cancer Therapeutic Paradigm

Janaki Neela Sharma, MD, assistant professor, clinical medicine, Genitourinary Medical Oncology, University of Miami Health Systems, discusses which trials have shifted the therapeutic paradigm for patients with urothelial cancer, specifically highlighting novel agents that have made a splash in this arena.

The phase 3 JAVELIN Bladder 100 trial (NCT02603432), an investigation with initial results published in 2020, enrolled patients with metastatic bladder cancer who had received first-line chemotherapy, Sharma begins. Following standard chemotherapy—typically cisplatin and gemcitabine at the time—patients were randomly assigned to receive either maintenance immunotherapy with avelumab (Bavencio) or best supportive care, which involved observation alone, she explains. The trial’s primary end point was overall survival (OS), and findings demonstrated a significant OS advantage with the use of immunotherapy following chemotherapy, Sharma reports. These results established a new standard of care in which immunotherapy serves as maintenance therapy after upfront chemotherapy for metastatic bladder cancer, she emphasized.

Subsequent notable advancements in bladder cancer management were limited until 2023, when the results of the phase 2 EV-103/KEYNOTE-869 trial (NCT03288545) of enfortumab vedotin-ejfv (Padcev) were reported, she continues. This dose-escalation and -expansion trial included multiple study arms, but a key focus was on patients with frontline metastatic bladder cancer who were ineligible for cisplatin, Sharma states, noting that the data revealed impressive progression-free survival and OS benefits vs chemotherapy in this patient subgroup.

The median OS in patients treated with frontline enfortumab vedotin plus pembrolizumab (Keytruda) reached 26.1 months, representing approximately a 30% improvement compared with traditional chemotherapy OS outcomes, she expands. Among cisplatin-ineligible patients, the most remarkable outcome was the observed overall response rate (ORR), which was 73.3%—substantially higher than the historical ORR of approximately 30% to 40% associated with conventional chemotherapy, Sharma emphasizes. These findings underscore enfortumab vedotin’s potential as a new therapeutic option with superior efficacy in the management of metastatic bladder cancer, she concludes.