Survival benefits were observed in patients considered hard to treat who received the antibody-drug conjugate enfortumab vedotin-ejfv (Padcev) for advanced urothelial carcinoma, according to results presented at the 2021 European Society for Medical Oncology Annual Congress.1
In the randomized phase 3 EV-301 trial (NCT03474107), enfortumab vedotin demonstrated superior overall survival (OS) compared with standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma.2 In July of this year, the FDA approved enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy; or patients who are ineligible for cisplatin-containing chemotherapy and have previously received 1 or more prior lines of therapy.3,4
“Effective therapies are still needed for advanced urothelial cancer, particularly pretreated patients with poor prognostic factors, such as liver metastases, and those who did not respond to prior immune checkpoint inhibitor treatment,” explained study author Jonathan Rosenberg, MD, chief of the Genitourinary Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York.
For the current study, investigators sought to evaluate the efficacy and safety of enfortumab vedotin in patients from EV-301 who were considered hard to treat. Hard-to-treat subgroups consisted of age 65 years or older, presence of liver metastasis, primary upper tract disease, and nonresponse to prior PD-1/L1 inhibitor treatment. The primary end point was OS and secondary end points were progression-free survival (PFS), and overall response rate (ORR) per RECIST v1.1, as well as safety.
The investigators found that OS was maintained across the majority of subgroups. Specifically, median OS in patients receiving enfortumab vedotin vs those receiving standard chemotherapy was as follows:
• Age 65 years or older: 14.32 vs 9.46 months (HR, 0.745; 95% CI, 0.558-0.995)
• Presence of liver metastasis: 9.63 vs 5.95 months (HR, 0.660; 95% CI, 0.456-0.957)
• Primary upper tract disease: 12.62 vs 10.91 months (HR, 0.848; 95% CI, 0.567-1.269)
• Nonresponse to prior PD-1/L1 inhibitor: 11.63 vs 9.17 months (HR, 0.757; 95% CI, 0.580-0.988).
Similar benefits were seen with median PFS in patients receiving enfortumab vedotin vs those receiving standard chemotherapy:
• Age 65 years or older: 5.65 vs 3.78 months (HR, 0.616; 95% CI, 0.485-0.781)
• Presence of liver metastasis: 4.14 vs 2.63 months (HR, 0.597; 95% CI, 0.428-0.833)
• Primary upper tract disease: 5.62 vs 3.78 months (HR, 0.716; 95% CI, 0.511-1.003)
• Nonresponse to prior PD-1/L1 inhibitor: 5.42 vs 3.65 months (HR, 0.697; 95% CI, 0.556-0.873).
ORR across the subgroups was also higher in patients receiving enfortumab vedotin compared with standard chemotherapy:
• Age 65 years or older: 40.8% vs 19.9%
• Presence of liver metastasis: 35.5% vs 10.8%
• Primary upper tract disease: 43.9% vs 19.0%
• Nonresponse to prior PD-1/L1 inhibitor: 39.7% vs 17.4%.
Regarding adverse events (AEs), overall rates were similar across the subgroups in both the enfortumab vedotin and standard chemotherapy cohorts. Treatment-related AEs were also comparable. When adjusted for treatment exposure, grade 3 or higher AEs occurred less frequently with patients receiving enfortumab vedotin vs those receiving standard chemotherapy across all subgroups.
“Based on these data, enfortumab vedotin shows consistent efficacy and safety in its use in this broad population of patients with previously treated advanced urothelial cancer, including those who might have hard-to-treat poor prognostic factors,” Rosenberg said.
1. Rosenberg JE, Powles T, Sonpavde GP, et al. Analysis of hard-to-treat subgroups from EV-301: A phase III trial of enfortumab vedotin (EV) vs chemotherapy for previously treated advanced urothelial carcinoma. Paper presented at 2021 European Society for Medical Oncology Annual Congress; September 16-21, 2021; virtual. Abstract 698P.
2. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384(2):1125-1135. doi:10.1056/NEJMoa2035807
3. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. March 9, 2021. News release. FDA. Accessed March 9, 2021. https://bit.ly/3jZoA4D
4. 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. Seagen Inc. March 9, 2021. Accessed March 9, 2021. https://bwnews.pr/3xxmsF9