Dr Bellmunt on the Impact of Treatment With Enfortumab Vedotin Plus Pembrolizumab in Urothelial Cancer

Joaquim Bellmunt, MD, PhD, associate professor of medicine, Harvard Medical School; director, Bladder Cancer Center, Genitourinary Oncology Program, Dana-Farber Cancer Institute, discusses the significance of the full FDA approval of treatment with enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma, highlighting how this decision has impacted global treatment recommendations for patients in the frontline setting.

The December 2023 FDA approval of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma marked a significant advancement in frontline therapy, Bellmunt begins. The decision was supported by data from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), in which the combination demonstrated a substantial overall survival (OS) benefit compared with traditional cisplatin- or carboplatin-based chemotherapy and was well tolerated, he reports. This led to its inclusion as a recommended frontline treatment regimen by the ESMO Guidelines Committee, of which Dr Bellmunt serves as a member.

The subsequent March 2024 FDA approval of nivolumab (Opdivo) plus cisplatin-based chemotherapy in first-line metastatic or unresectable urothelial carcinoma, supported by data from the phase 3 CheckMate 901 trial (NCT03036098), provided additional options for frontline treatment, Bellmunt continues. The significant improvement in median OS that was achieved with this triplet regimen underscores the evolving landscape of immunotherapy-based approaches in bladder cancer management, he states.

These trials provide level 1 evidence of a survival advantage when using immunotherapy-based approaches vs traditional chemotherapy, Bellmunt says. Although cross-trial comparisons cannot be performed, the consensus that emerged from these investigations supported enfortumab vedotin plus pembrolizumab as the optimal frontline therapy based on its substantial survival benefit, he details. This recommendation considers the broad initial approval and consistent benefit observed with the regimen across various patient subgroups, Bellmunt expands.

Despite the regimen’s proven efficacy, challenges remain regarding access to approved therapies globally. Bellmunt adds that there are several European countries where enfortumab vedotin plus pembrolizumab may not yet be available. Alternative induction-maintenance strategies, such as chemotherapy followed by maintenance avelumab (Bavencio) or cisplatin-based combinations with nivolumab offer viable options for patients unable to receive the preferred regimen, he says.

Overall, the incorporation of these novel combinations into treatment guidelines reflects a paradigm shift in bladder cancer management, emphasizing the importance of tailored approaches to optimize patient outcomes and address unmet needs in different health care settings, Bellmunt concludes.