Jonathan Rosenberg, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses results from a phase 3 trial comparing enfortumab vedotin and chemotherapy in locally advanced or metastatic urothelial carcinoma who received a prior platinum-containing chemotherapy and had disease progression during or after PD-1/L1 inhibitor treatment.
These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.
My name is Dr. Jonathan Rosenberg. I'm a medical oncologist at Memorial Sloan Kettering where I lead the Genitourinary Cancer Oncology Program. It's my pleasure today to talk to you about the results of the phase 3, randomized trial for enfortumab vedotin or standard chemotherapy in patients with metastatic disease.
Enfortumab vedotin was developed as an antibody drug conjugate targeting the molecule Nectin‑4, which is expressed on the vast majority of urothelial cancer cells. It was shown in phase 1 and 2 studies to have an objective response rate of about 40%, which led to the development of the randomized phase 3 trial.
Enfortumab vedotin was FDA‑approved as an accelerated approval based on the phase 2 study, EV‑201, which was published in the Journal of Clinical Oncology. This was then followed up with the randomized phase 3 trial presented at Genitourinary Cancers Symposium and published in The New England Journal on the same day in 2021.
This trial randomized patients to enfortumab vedotin administered at a dose of 1.25 mg/kg intravenously on days 1, 8, and 15 every 28 days, or standard chemotherapy, which in the United States was a paclitaxel or docetaxel, or vinflunine if they were treated in Europe.
Over 600 patients were randomized to either of these arms in a 1:1 fashion. Patients were treated until disease progression. The study showed an improvement in overall survival of patients treated with enfortumab vedotin with a hazard ratio of 0.7 in an approximately 4‑month improvement in median survival.
The toxicity profile was similar to what was seen in prior phase 2 studies with fatigue, peripheral neuropathy, and rash being the most prominent toxicities, although rare cases of severe hyperglycemia and more severe skin rashes were observed.
These results, I believe, are practice‑changing and confirmed that in patients who have had prior chemotherapy and immunotherapy should be suggested to receive enfortumab vedotin in the third‑line setting based on the results of EV‑301.
It's likely that the FDA will approve EV‑301 fully in the United States and that it will also lead to approval in Europe for this patient population. Further research is looking towards treating patients in earlier lines of therapy, either as monotherapy or in combination with pembrolizumab.
The combination with pembrolizumab has received FDA breakthrough therapy designation but has not yet been approved in the United States. Further research is ongoing. Thank you very much.
Powles T, Rosenberg JE, Sonpavde G, et al. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 393.
Dr Rosenberg has served as a consultant for Seattle Genetics, Astellas, Merck, BMS, AstraZeneca, Bayer, Roche/Genentech, Mirati, GSK, Boehringer Ingelheim, Janssen, Pfizer, EMD-Serono, and Lilly.