Dr Petrylak on the Shifting Role of Avelumab Maintenance in Metastatic Urothelial Cancer

Commentary
Video

Daniel Petrylak, MD, discusses how the FDA approval of enfortumab vedotin plus pembrolizumab impacts the use of avelumab maintenance in urothelial cancer.

Daniel Petrylak, MD, professor, medicine, (medical oncology) and urology, chief, Genitourinary Oncology, Yale School of Medicine, discusses how the role of avelumab (Bavencio) maintenance therapy in metastatic urothelial cancer has been affected by the FDA approval of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for this indication.

In December 2023, enfortumab vedotin plus pembrolizumab was approved by the FDA for the treatment of patients with locally advanced or metastatic urothelial cancer. The regulatory decision was supported by data from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), in which this combination produced a statistically significant and clinically meaningful survival benefit vs standard-of-care (SOC) chemotherapy and was associated with manageable safety profile.

Prior to the readout of the EV-302 trial, avelumab maintenance therapy had been the established SOC following platinum-containing chemotherapy, Petrylak begins. However, the EV-302 combination leverages enfortumab vedotin, a superior and highly potent cytotoxic agent, he states. Prior research has shown efficacy with enfortumab vedotin in patients with visceral disease, with the agent eliciting response rates of approximately 40% in the liver across the first-, second-, and third-line settings, Petrylak reports. When combined with pembrolizumab, which functions as maintenance therapy upon continuation, enfortumab vedotin presents a promising treatment approach for patients with locally advanced or metastatic urothelial cancer, Petrylak explains.

In the context of patients undergoing treatment with enfortumab vedotin plus pembrolizumab, chemotherapy followed by avelumab maintenance therapy may have a decreased role, Petrylak asserts. At this time, Petrylak states that he may only consider the upfront administration of gemcitabine plus cisplatin or carboplatin for patients who are unsuitable for enfortumab vedotin, possibly due to peripheral neuropathy or uncontrolled diabetes.

Furthermore, caution is advised in administering maintenance therapy, as well as enfortumab vedotin plus pembrolizumab, to patients with pre-existing autoimmune disorders that might be exacerbated by checkpoint inhibition, Petrylak adds. Despite this, there remains a discernible, albeit limited, role for maintenance therapy after first-line cytotoxic treatment in metastatic urothelial carcinoma, he concludes.

Related Videos
Kathleen A. Dorritie, MD
David L. Porter, MD, director, Cell Therapy and Transplant, Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Penn Medicine
Muhamed Baljevic, MD
Sumanta Kumar Pal, MD, FASCO,
Carrie L. Kitko, MD
Kara N. Maxwell, MD, PhD
Kian-Huat Lim, MD, PhD
Thomas F. Gajewski, MD, PhD
Michelle Krogsgaard, PhD
Lori A. Leslie, MD