#0585

Enfortumab Vedotin Plus Pembrolizumab Versus Chemotherapy in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma: Updated Analysis of the Pan-Asian Subgroup from EV-302/KEYNOTE-A39

J. Li¹, E. Kikuchi², M. Heijden³, B. Valderrama⁴, S. Gupta⁵, J. Bedke⁶, S. Shin⁷, J. Guo⁸, P. Danchaivijitr⁹, R. Kanesvaran¹⁰, S. Park¹¹, W. Su¹², S. Kandori¹³, W. Bae¹⁴, A. Wong¹⁵, Y. Lu¹⁶, X. Yu¹⁶, S. Gorla¹⁷, A. Bavle¹⁸, T. Powles¹⁹

¹Taichung Veterans General Hospital, Urology, Taichung, Taiwan
²St. Marianna University School of Medicine, Department of Urology, Kanagawa, Japan
³Netherlands Cancer Institute, Medical Oncology Department, Amsterdam, Netherlands
⁴Hospital Universitario Virgen del Rocio, Department of Medical Oncology, Seville, Spain
⁵Taussig Cancer Center-Cleveland Clinic, Medicine Department, Cleveland, OH, United States
⁶Klinikum Stuttgart – Katharinenhospital (KH), Urology Department, Stuttgart, Germany
⁷Yonsei University College of Medicine, Medical Oncology Department, Seoul, Korea (Republic of)
⁸Peking University Cancer Hospital and Institute, Department of Renal Cancer and Melanoma, Beijing, China
⁹Siriraj Hospital, Mahidol University, Division of Medical Oncology, Faculty of Medicine, Bangkok, Thailand
¹⁰NCCS - National Cancer Centre Singapore, Division of Medical Oncology, Singapore, Singapore
¹¹Samsung Medical Center (SMC) – Sungkyunkwan University School of Medicine, Hematology and Oncology, Seoul, Korea (Republic of)
¹²NCKUH - National Cheng Kung University Hospital, Department of Internal Medicine, Tainan, Taiwan
¹³University of Tsukuba, Urology, Tsukuba, Japan
¹⁴Chonnam National University Hwasun Hospital, Oncology Department, Hwasun, Korea (Republic of)
¹⁵National University Cancer Institute, Haematology Oncology, Singapore, Singapore
¹⁶Pfizer, Clinical Development, San Diego, CA, United States
¹⁷Astellas Pharma USA, Oncology, Northbrook, IL, United States
¹⁸Merck & Co. Inc – MRL Labs – Upper Gwynedd Campus, Clinical Research, North Wales, PA, United States
¹⁹St. Bartholomew’s Hospital – Barts Health NHS Trust, Oncology Department, London, United Kingdom

Introduction:

Primary results from the phase 3 EV-302 study in first-line locally advanced/metastatic urothelial cancer (la/mUC) demonstrated statistically significantly longer overall survival (OS) and progression-free survival (PFS) with enfortumab vedotin + pembrolizumab (EV+P) vs chemotherapy (chemo) in the overall population and improved outcomes in a post hoc analysis of patients from Asia. Based on these results, EV+P is considered the new standard of care for first-line la/mUC. In an updated analysis with ~2.5 years of median follow-up, EV+P continued to show superior efficacy vs chemo, consistent with the primary analysis. Here, we present updated results from the pan-Asian subgroup analysis.

Material and methods:

This analysis included patients from China, Japan, South Korea, Singapore, Thailand and Taiwan. Eligible adult patients had unresectable Ia/mUC that was previously untreated with PD-(L)1 inhibitors or other systemic therapy. Patients were randomly assigned 1:1 to receive 3-week cycles of EV (IV 1.25 mg/kg on days 1 and 8) + P (IV 200 mg on day 1) or chemo (gemcitabine with cisplatin or carboplatin). Dual primary endpoints were PFS by blinded independent central review per Response Evaluation Criteria in Solid Tumors v1.1, and OS. Secondary endpoints included objective response rate (ORR) and safety.

Results:

From 886 patients randomized, 176 were enrolled in Asia and included in this analysis (EV+P, n=94; chemo, n=82). Patient characteristics were similar between arms and broadly similar to the overall population. At data cutoff (8 Aug 2024), median (95% CI) follow-up was 28.1 (26.5, 29.2) months. Median PFS was longer with EV+P (23.8 months) vs chemo (6.3 months) with a 63% decrease in the risk of progression or death (HR [95% CI]: 0.37 [0.24, 0.57]). Median OS was not estimable for EV+P vs 18.0 months for chemo, with a 67% decrease in the risk of death (HR [95% CI]: 0.33 [0.20, 0.54]). Confirmed ORR was 72.2% for EV+P vs 35.0% for chemo. Grade ≥3 TRAEs occurred in 66.0% and 68.4% of patients in the EV+P and chemo arms, respectively. Grade ≥3 TRAEs of special interest for EV included skin reactions (28.7%), hyperglycemia (10.6%) and peripheral neuropathy (8.5%); 13.8% and 5.3% of patients discontinued EV due to treatment-related peripheral neuropathy or skin reactions, respectively; none discontinued EV due to hyperglycemia. Grade ≥3 treatment-emergent AEs of special interest for P included severe skin reactions (18.1%) and pneumonitis (7.4%); 8.5% of patients discontinued P due to treatment-emergent pneumonitis; none discontinued P due to severe skin reactions.