Treatment with Padcev, compared to chemotherapy, continues to show better results in patients with advanced urothelial carcinoma who had previously received certain therapies.
Treatment with Padcev (enfortumab vedotin-efjv) continues to be associated with better survival outcomes and responses to therapy in patients with advanced urothelial carcinoma who had previously received platinum-based chemotherapy and PD-1/PD-L1 inhibitors, compared to chemotherapy.
“(Padcev) is the first drug beyond chemotherapy and immunotherapy to show a significant survival advantage in previously treated advanced urothelial cancer,” said Dr. Thomas Powles, director of the Barts Cancer Centre in London, United Kingdom, in a presentation of the data during the virtual 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium. “This is a big step in the right direction for patients with advanced urothelial cancer, where treatment options remain quite limited.”
Padcev received Food and Drug Administration (FDA) approval in December 2019 for the treatment of adults with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy. The accelerated approval was granted because treatment options are limited once urothelial cancer has progressed on both chemotherapy and immunotherapy. Data from the phase 2 EV-201 trial supported the approval.
This data comes from the open-label, randomized phase 3 EV-301 trial, which served as a confirmatory study for the benefit of Padcev over chemotherapy in this setting following the FDA approval.
A total of 608 patients (median age, 68 years) with histologically or cytologically confirmed urothelial cancer, including patients with squamous differentiation or mixed cell types, were enrolled onto the study, and randomized to receive either Padcev (301 patients) or chemotherapy (307 patients). Eligible patients had radiographic progression or relapsed during or after immune checkpoint inhibition for the treatment of advanced urothelial cancer and had received prior platinum-containing chemotherapy.
Patients in the chemotherapy arm received either docetaxel, paclitaxel or vinflunine.
Measuring overall survival (OS) was the main goal of the study. Other goals included assessing progression-free survival (the time from treatment to disease progression or worsening), objective response rates (the proportion of patients who had a complete or partial response to treatment) and safety.
Fourteen percent of the patient population was from the United States, 31% had liver metastases and 87% had received one or two previous lines of therapy.
As of data cutoff, 81% of patients had discontinued treatment in the Padcev arm versus 93% in the chemotherapy arm, which was due to progressive disease in 59% of patients in both arms. At a median follow-up of 11.1 months, the median treatment exposure was 5 months in the Padcev and 3.5 months in the chemotherapy arm.
The median OS with Padcev was 12.88 months versus 8.97 months with chemotherapy. Subgroup analyses for OS favored the Padcev arm for all groups except women, although Powles noted that some of the subgroups were too small to draw conclusions.
Median progression-free survival with Padcev was 5.55 months versus 3.71 months.
Confirmed objective response rate in the Padcev arm was 40.6%, which included complete responses in 4.9% of patients. In the chemotherapy arm, the objective response rate was 17.9% with complete responses in 2.7% of patients.
Treatment-related adverse event (TRAE) rates were similar between the two arms, with any-TRAE rates of 94% in the Padcev arm and 92% in the chemotherapy arm, and grade 3 or higher (more serious or severe) TRAE rates of 51% and 50%, respectively. TRAEs led to treatment discontinuation in 14% of patients in the Padcev arm and 11% in the chemotherapy arm.
Powles highlighted that the rate of grade 3 or higher maculopapular rash (flat and raised skin lesions) was increased in the Padcev arm (7% vs. 0%), whereas rates of grade 3 or higher neutrophil count decrease (6% vs 13%), white blood cell count decrease (1% vs 7%), and febrile neutropenia (1% vs 6%) were all higher in the chemotherapy arm.
TRAEs of special interest in the Padcev arm included rash (all grade, 44%; grade 3 or higher, 15%) and severe cutaneous adverse reactions (all grade, 20%; grade 3 or higher, 5%), peripheral neuropathy in terms of sensory events (all grade, 44%; grade 3 or higher, 4%) and motor events (all grade, 7%; grade 3 or higher, 2%), and hyperglycemia (all grade, 6%; grade 3 or higher, 4%). The majority of TRAEs of special interest were mild to moderate in severity.