FDA Expands Indication, Grants Regular Approval for Urothelial Cancer Therapy

The FDA granted accelerated approval in 2019 to enfortumab vedotin-ejfv for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before or after surgery, or in a locally advanced or metastatic urothelial cancer setting.

Officials with the FDA have expanded the approved indication for enfortumab vedotin-ejfv (Padcev; Astellas) to include adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received 1 or more prior lines of therapy. According to Astellas, the action announced Friday also included the FDA’s decision to grant the drug regular approval status.

The FDA granted accelerated approval in 2019 to enfortumab vedotin-ejfv for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before or after surgery, or in a locally advanced or metastatic urothelial cancer setting. The conversion from accelerated approval to regular approval and the label expansion were based on 2 supplemental Biologics License Applications that were reviewed under the Real-Time Oncology Review pilot program.

"The FDA's decision to convert accelerated approval to regular approval was based on data from the phase 3 EV-301 trial, which had a primary endpoint of overall survival for patients treated with [enfortumab vedotin-ejfv] versus chemotherapy," said Andrew Krivoshik, MD, PhD, Senior Vice President and Oncology Therapeutic Area Head, Astellas, in a press release. "With [enfortumab vedotin-ejfv], for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy."

According to Astellas, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually worldwide. Patients who are ineligible for cisplatin-containing chemotherapy typically have limited treatment options and a poor prognosis.

The EV-301 trial compared enfortumab vedotin-ejfv to chemotherapy in adult patients (n=608) with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of pre-specified interim analysis, patients who received enfortumab vedotin-ejfv (n=301) in the trial lived a median of 3.9 months longer than those who received chemotherapy (n=307). Median overall survival was 12.9 vs. 9.0 months, respectively [Hazard Ratio=0.70 (95% CI: 0.56, 0.89), p=0.001].

The most common all-grade adverse reactions (≥20%) reported in the EV-301 trial included rash, fatigue, peripheral neuropathy, alopecia, decreased appetite, diarrhea, pruritus, nausea, constipation, dysgeusia, musculoskeletal pain, dry eye, pyrexia, abdominal pain, and anemia.

Cohort 2 of the EV-201 trial evaluated enfortumab vedotin-ejfv in patients (n=89) with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/L1 inhibitor, had not received a platinum-containing chemotherapy in this setting, and were ineligible for cisplatin. After a median follow-up of 16 months, 51% of patients who received enfortumab vedotin-ejfv had an objective response [95% CI: 39.8, 61.3] per blinded independent central review, with a median duration of response of 13.8 months [95% CI: 6.4, not reached].

The most common all-grade adverse reactions (≥20%) reported in the EV-201 trial included rash, peripheral neuropathy, alopecia, fatigue, decreased appetite, anemia, diarrhea, pruritus, weight decreased, nausea, dry eye and dysgeusia.

"Almost half of [patients with advanced bladder cancer] cannot receive cisplatin-based chemotherapy. Many of these patients will receive first-line immunotherapy. If their cancer does not respond—or if it progresses after prior response to immunotherapy—there is an urgent need for more treatment options as there is currently no standard of care," said Evan Y. Yu, MD, Division of Oncology, Department of Medicine, University of Washington School of Medicine and a lead investigator for the EV-201 trial, in a press release. "A new regulatory approval for enfortumab vedotin-ejfv is an important clinical advance and can help serve this unmet need."

REFERENCE

U.S. FDA grants regular approval and expands indication for Padcev (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer [news release]. July 9, 2021; Astellas. [email]