The combination of enfortumab vedotin and pembrolizumab elicited a high overall response rate and a manageable safety profile in patients with locally advanced or metastatic urothelial cancer.
The combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) elicited a high overall response rate (ORR) and a manageable safety profile in patients with locally advanced or metastatic urothelial cancer, according to data from Cohort K of the phase 1/2 EV-103 trial (NCT03288545), presented at the 2022 ESMO Congress.
“Enfortumab and pembrolizumab as monotherapy have each shown anti-tumor activity with a survival benefit in pretreated patients with locally advanced or metastatic urothelial cancer. Enfortumab vedotin/pembrolizumab was previously evaluated in the EV-103 dose escalation/Cohort A, which showed encouraging safety and efficacy activity with a response rate of 73.3%,” said Jonathan E. Rosenberg, MD, chief of the Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, and Enno W. Ercklentz Chair at Memorial Sloan Kettering Cancer Center in New York, New York.2
For the current study, “previously untreated cisplatin-ineligible patients with [locally advanced or metastatic urothelial cancer] were randomly assigned 1:1 to enfortumab vedotin (1.25.mg/kg) as monotherapy on Days 1 and 8 or in combination with P (200 mg) on Day 1 of 3-week cycles,” the authors wrote in their abstract. The primary end point was confirmed ORR by blinded independent central review. Duration of response (DOR) and safety were among the secondary end points.
In his presentation, Rosenberg stressed that the study was non comparative.
“We are not planning and we will not be performing any statistical comparisons formally between the arms. This study was really to understand the contribution of components of the different agents,” Rosenberg explained.
The patient population was predominantly male, and approximately 60% had impaired performance status. Visceral disease was presented more than 80% of patients, and approximately 40% were PD-L1 high; a proportion of patients were not evaluable because they did not have tumor to be submitted.
A total of 149 patients were included in the study, 76 of whom were treated with enfortumab vedotin plus pembrolizumab and 73 who were treated with enfortumab vedotin alone. The confirmed ORR (95% CI) for enfortumab vedotin plus pembrolizumab was 64.5%, and median DOR was not reached. Confirmed ORR for enfortumab vedotin alone was 45.2%, with a median DOR (95% CI) of 13.2 months.
Regarding adverse events (AEs), 15.6% of patients receiving enfortumab vedotin plus pembrolizumab stopped treatment due to an AE, and 24.3% of patients receiving enfortumab vedotin alone stopped treatment due to an AE. The most common AEs seen in patients receiving enfortumab vedotin plus pembrolizumab included fatigue, peripheral sensory neuropathy, alopecia, and maculo-papular rash. Eighteen (23.7%) serious treatment-related adverse events (TRAEs) were seen in the combination therapy group and 11 (15.1%) were seen in the monotherapy group. Three TRAEs leading to death (3.9%) were seen in the combination group and 2 (2.7%) were seen in the monotherapy group. Rosenberg reported that skin reactions were more frequent with patients receiving enfortumab vedotin plus pembrolizumab, although none were serious.
“Results from EV-103/KEYNOTE-869 Cohort K support the ongoing investigation of enfortumab vedotin and pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who are in need of treatment options, and this combination may be an important therapeutic option for these patients,” Rosenberg said in a news release about the study.3