In patients with metastatic urothelial carcinoma, platinum chemotherapy is the standard of care in the first-line setting; however, for patients who are ineligible for platinum treatment, the alternative standard—gemcitabine plus carboplatin—can be poorly tolerated and have limited durability and survival. Therefore, Study EV-103 was undertaken to examine whether the immune checkpoint inhibitor pembrolizumab in combination with the antibody-drug conjugate enfortumab vedotin may be an alternative option for platinum-ineligible patients with locally advanced or metastatic urothelial carcinoma.
Jonathan E. Rosenberg, MD
Results of a preliminary durability analysis were presented by Jonathan E. Rosenberg, MD, and colleagues at the 2020 Genitourinary (GU) Cancers Symposium (Abstract 441).
Methodology
As of October 2019, 45 patients (median age = 69 years) with locally advanced or metastatic urothelial carcinoma who were ineligible for platinum-based treatment received 1.25 mg/kg of enfortumab vedotin (days 1 and 8) plus pembrolizumab (day 1). The primary endpoint was safety/tolerability.
Patients received a median of nine cycles of enfortumab vedotin/pembrolizumab.
KEY POINTS
- Enfortumab vedotin/pembrolizumab led to an objective response rate of 73%, including a complete response rate of 15.6%; the disease control rate was 93.3%.
- Of 33 responders, 18 have ongoing responses, and there are 11 responses that are longer than 10 months.
The most common treatment-emergent adverse events were fatigue (58%; 11%, at least grade 3), alopecia (53%), and peripheral sensory neuropathy (53%; 4%, at least grade 3). One patient died due to an adverse event reported as related (multiple organ failure). Enfortumab vedotin/pembrolizumab led to an objective response rate of 73% (95% confidence interval = 58.1%–85.4%), including a complete response rate of 15.6%; the disease control rate was 93.3%. Progression-free survival was 12.3 months, and overall survival at 1 year was 81.6%. Median duration of response has not been reached. Of 33 responders, 18 (55%) have ongoing responses, and there are 11 responses that are longer than 10 months.
The study authors concluded, “In first-line cisplatin-ineligible pts with metastatic urothelial carcinoma, enfortumab vedotin/pembrolizumab, a potential platinum-free option, demonstrates promising activity and durability, with a manageable safety profile. Further evaluation of enfortumab vedotin/pembrolizumab in metastatic urothelial carcinoma and muscle-invasive urothelial carcinoma is ongoing.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
