269O - Enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Pan-Asian subgroup analysis from EV-302/KEYNOTE-A39

Background

In the phase III EV-302 study, EV+P demonstrated statistically significantly prolonged overall survival (OS) and progression-free survival (PFS) vs chemo in patients (pts) with previously untreated la/mUC. Here, we present a post hoc pan-Asian subgroup analysis of EV-302.

Methods

Pts with previously untreated la/mUC were randomly assigned 1:1 to receive 3-week cycles of EV (1.25 mg/kg; IV) on Days 1 and 8 and P (200 mg; IV) on Day 1 or gemcitabine with cisplatin or carboplatin (chemo). Dual primary endpoints were PFS per RECIST v1.1 by BICR and OS. Select secondary endpoints included objective response rate (ORR) and safety. Pts from China, Japan, Korea, Singapore, Thailand, and Taiwan were included in this analysis.

Results

In EV-302, 886 pts were randomly assigned; 176 pts (EV+P: 94; chemo: 82) were from Asian countries, and pt characteristics were balanced between arms. At data cutoff (8 Aug 2023), median follow-up time was 15.6 months. For the pan-Asian subgroup, median PFS was prolonged with EV+P vs chemo, reducing the risk of progression or death by 70% (HR 0.30; [95% CI: 0.19–0.48]). For median OS, EV+P reduced the risk of death by 66% (HR 0.34; [95% CI: 0.18–0.65]) vs chemo. Confirmed ORR was 72.2% and 35.0% in EV+P and chemo arms, respectively. Grade (G) ≥3 treatment-related adverse events (TRAEs) occurred in 64.9% with EV+P and 68.4% with chemo. Most common G ≥3 TRAEs were maculopapular rash (11.7%), hyperglycemia (10.6%), and peripheral sensory neuropathy (7.4%) for EV+P, and neutropenia (25.0%), anemia (19.7%), and neutrophil count decreased (18.4%) for chemo. Most common G ≥3 TRAEs of special interest for EV were skin reactions (27.7%), hyperglycemia (10.6%), and peripheral neuropathy (8.5%). Most common G ≥3 treatment-emergent AEs of special interest for P were severe skin reactions (18.1%) and pneumonitis (6.4%).

Conclusions

Consistent with results of the overall EV-302 population, this pan-Asian subgroup analysis showed that EV+P improved outcomes in pts with previously untreated la/mUC, and the safety profile was generally manageable. These results further support EV+P as a new first-line treatment for pts with la/mUC.

Clinical trial identification

NCT04223856.

Editorial acknowledgement

Medical writing support, conducted wih the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Steven F. Merkel, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA.

Legal entity responsible for the study

The EV-302 study was funded by Astellas Pharma Inc., Northbrook, IL, USA; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; and Seagen Inc., Bothell, WA, USA, which was acquired by Pfizer in December 2023.

Funding

Astellas Pharma Inc.

Disclosure

E. Kikuchi: Financial Interests, Personal, Invited Speaker: MSD, Bristol, Janssen, Astellas, Merck Biopham, Nippon Kayaku, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas, MSD, Bristol, Janssen, Merck Biopham; Financial Interests, Institutional, Research Grant: Takeda, Nippon Kayaku, Kyorin, Taiho, Nippon Shinyaku. M.S. van der Heijden: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Seagen, Pfizer, Astellas; Financial Interests, Institutional, Funding, Investigator-initiated trial: BMS, Roche, AstraZeneca, 4SC, MSD; Financial Interests, Institutional, Steering Committee Member, Local PI + SSC member: BMS, AstraZeneca, MSD, Seagen; Financial Interests, Institutional, Steering Committee Member, Local PI + study co-PI: Janssen. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, Bristol-Myers-Squibb, Ipsen, EUSA Pharma, Merck, MSD, Astra-Zeneca, AAA, Recordati; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Bayer, MSD, Merck, Pfizer, Astellas Pharma, AAA, Almirall pharma; Other, Personal, Other, Travel/accommodation: Bristol--Myers-Squibb, Pfizer. S. Gupta: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Bristol Myers Squibb, EMD Serono, Pfizer, Seattle Genetics, Astellas, Bayer, Genzyme, Foundation medicine, Gilead, Loxo Oncology ; Financial Interests, Personal, Stocks/Shares: Moderna, Nektar Therapeutics , BioNTech. J. Bedke: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Eisai; Financial Interests, Personal, Advisory Board, Advisory Board and Speaker´s Bureau: BMS, Ipsen, MSD, Merck Sorono, Pfizer, Roche, Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, Eisai, Novartis, Nektar; Financial Interests, Institutional, Coordinating PI: Astellas, BMS, MSD, Ipsen, Pfizer, Roche, Seagen; Financial Interests, Institutional, Steering Committee Member: BMS, MSD, Pfizer, Seagen; Other, Personal, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology. J. Guo: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Roche, Bayer, Novartis, Simcere Pharmaceutical Group , Shanghai Junshi Biosciences, Oriengene. P. Danchaivijitr: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Roche, AstraZeneca, Astellas, Research University Network of Thailand; Financial Interests, Personal, Other, Lectures: Roche, AstraZeneca, Astellas, Janssen, BMS. R. Kanesvaran: Financial Interests, Institutional, Invited Speaker: Astellas, Johnson and Johnson, Ipsen, Amgen, BMS, MSD, Novartis, AstraZeneca, Sanofi, Merck; Financial Interests, Institutional, Advisory Board: Johnson and Johnson, Pfizer, Ipsen, Amgen, BMS, MSD, Bayer, AstraZeneca, Ferring; Financial Interests, Institutional, Research Grant: Sanofi, Eisai, Johnson and Johnson; Non-Financial Interests, Personal, Leadership Role, Past President: Singapore Society of Oncology, SIOG; Non-Financial Interests, Personal, Leadership Role, Vice Chairman: Singapore Cancer Society; Non-Financial Interests, Personal, Leadership Role, Medical Advisory Board Member: International Kidney Cancer Coalition. A.S. Wong: Financial Interests, Personal, Advisory Board: The authors. J. Lu, X. Yu: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. A. Shetty: Financial Interests, Institutional, Full or part-time Employment: Astellas. A.A. Bavle: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers-Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Other, honoraria: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers-Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Other, Honoraria: Gilead. All other authors have declared no conflicts of interest.