698P - 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

Background

Effective therapies are critically needed for previously treated patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC), particularly those considered hard-to-treat with poor prognostic factors. In the phase III EV-301 trial (NCT03474107), EV showed superior overall survival (OS) compared with standard chemotherapy (SC) in pts with previously treated la/mUC; this subgroup analysis evaluates the efficacy and safety of EV for those with poor prognostic factors.

Methods

In this open-label, phase III trial, la/mUC pts previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor were randomized 1:1 to EV or investigator’s choice of SC (docetaxel, paclitaxel, vinflunine). Subgroup analyses were prespecified for the primary endpoint of OS and secondary endpoints of investigator-assessed progression-free survival (PFS) and overall response rate (ORR) per RECIST v1.1. Kaplan-Meier analyses compared OS and PFS between treatments for selected hard-to-treat subgroups: age ≥65 years, presence of liver metastasis, primary upper tract disease, and checkpoint inhibitor (CPI) nonresponse. ORR and safety were also evaluated within subgroups.

Results

As of July 15, 2020, 301 pts were randomized to EV and 307 pts to SC; median follow-up was 11.1 months. OS benefit of EV was retained across most hard-to-treat subgroups with longer median OS in pts on EV vs SC (Table). PFS and ORR benefit was also observed across most subgroups for EV vs SC. Overall rates of treatment-emergent and -related adverse events were comparable between treatments across subgroups.

Conclusions

Hard-to-treat pts with la/mUC had consistently longer OS and PFS and higher ORR with EV vs SC; safety profiles for study treatments were consistent with those of prior studies. These data support EV use in previously treated pts with la/mUC, including those with poor prognostic factors. Table: 698P

^an/N (%). ^bMedian for OS, PFS.

Clinical trial identification

NCT03474107.

Editorial acknowledgement

Writing and editorial assistance was provided by Stephanie Phan, PharmD, Cheryl Casterline, MA, and Elizabeth Hermans, PhD, from Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by the study sponsors.

Legal entity responsible for the study

Astellas Pharma, Inc. and Seagen Inc.

Funding

This study is sponsored by Astellas Pharma, Inc. and Seagen Inc.

Disclosure

J.E. Rosenberg: Financial Interests, Institutional, Other, Clinical Trial Funding: Astellas, Roche, Genentech, AstraZeneca, Bayer, Seattle Genetics, QED; Financial Interests, Institutional, Other, Consulting Fees: Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, EMD-Serono, Gilead/Immunomedics, GSK, Janssen, Lilly, Merck, Mirati, Pfizer, QED, Roche/Genentech, Seattle Genetics, and Tyra Biosciences. T. Powles: Financial Interests, Institutional, Funding, Grant/Funding to Institution: AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Advisory Board, Advisory/Research Boards: AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche; Financial Interests, Institutional, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen. G.P. Sonpavde: Financial Interests, Personal, Other, consultant: Seattle Genetics; Financial Interests, Personal, Other, consultant (fees/year comply with my institution's guidelines) and research support to institution: Genentech, Merck; Financial Interests, Personal, Research Grant, consultant (fees/year comply with my institution's guidelines): Sanofi; Financial Interests, Personal, Other, consultant (fees/year comply with my institution's guidelines): Seattle Genetics/Astellas,Exelixis; Financial Interests, Personal, Other, consultant; Member of data safety monitoring board; steering committee,travel: AstraZeneca; Financial Interests, Personal, Other, Author of educational chapter/review (fees/year comply with my institution's guidelines): Uptodate; Financial Interests, Personal, Other, consultant; steering committee of trial sponsored by BMS; travel support for investigator meetings: Bristol-Myers-Squibb (BMS); Financial Interests, Personal, Invited Speaker, CME certified conference speaker: Physicians Education Resource; Financial Interests, Personal, Invited Speaker, Conference speaker: Onclive; Financial Interests, Personal, Invited Speaker, Speaker in CME-certified educational meeting: Research to Practice; Financial Interests, Institutional, Other, steering committee of trial sponsored by Bavarian Nordic: Bavarian Nordic,Debiopharm; Financial Interests, Personal, Research Grant, Research support to institution and steering committee of trial sponsored by QED: QED; Financial Interests, Personal, Invited Speaker, Speaker of CME certified webcast: Medscape; Financial Interests, Personal, Other, consultant (fees/year comply with my institution's guidelines): Eisai, Bicycle Therapeutics, Dava oncology,EMD Serono/Pfizer. Y. Loriot: Financial Interests, Institutional, Research Grant: Jannsen, Celsius, MSD; Financial Interests, Personal, Other, Support for attending meetings and/or travel: BMS, Roche, AstraZeneca, MSD, Pfizer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, Pfizer, Merck Kg, MSD, AstraZeneca, Roche, Janssen, Astellas, Seattle Genetics, Immunomedics; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, Pfizer, Janssen, Merck Kg. I. Duran: Financial Interests, Institutional, Research Grant: Roche, AstraZeneca; Financial Interests, Institutional, Other, Honoraria for lectures: Astellas, Msd, Merck-Pfizer, AstraZeneca, Bms, Roche, Janssen; Financial Interests, Institutional, Other, Payment for educational event: Janssen; Financial Interests, Institutional, Other, Meeting travel support/registration: AstraZeneca, Ipsen; Financial Interests, Institutional, Other, Meeting registration: Pfizer; Financial Interests, Institutional, Advisory Board: Astellas, Msd, Merck, Immunomedics, Roche; Financial Interests, Institutional, Other, Co-founder and president of this GU oncology cooperative group: Go Norte Oncology Group. N. Matsubara: Financial Interests, Personal, Speaker’s Bureau: Janssen, Sanofi; Financial Interests, Personal, Advisory Board: Janssen, Sanofi, AstraZeneca, Roche,; Financial Interests, Institutional, Research Grant: Janssen, AstraZeneca, Takeda, Lilly, Amgen, Astellas, Chugai, Bayer, MSD, Ono, Taiho, Pfizer. C. Vulsteke: Financial Interests, Institutional, Other, Consultancy: Janssen-Cilag, Roche, GSK, Atheneum Partners, Astellas Pharma, MSD, BMS, Leo-Pharma; Financial Interests, Institutional, Advisory Board, Presentation and Advisory Board: Janssens Cilag, Leo Pharma; Financial Interests, Institutional, Advisory Board, Presentation: Bayer; Financial Interests, Institutional, Advisory Board: Merck, MSD, GSK, AstraZeneca; Financial Interests, Personal, Other, Travel: Roche Pfizer. D. Castellano: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, BMS, Clovis, Eisai, Exelisis, GSK, Ipsen, Janssen, Lilly, MSD, Pfizer, QED Therapeutics, Roche; Financial Interests, Institutional, Other, Local Pi: Astellas, AstraZeneca, BMS, GSK, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche; Non-Financial Interests, Institutional, Other: Astellas, AstraZeneca, BMS, GSK, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Bayer, Eisai, Exelsis, Lilly, Pfizer, QED Therapeutics; Non-Financial Interests, Personal, Other: SOGUG (Spanish Oncology Genito-Urinary Group) Foundation, Other, Executive member. R. Mamtani: Financial Interests, Personal, Other, Consulting Fees: Roche, Astellas, Seagen; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Speaker’s Bureau: Flatiron Health. S.S. Sridhar: Financial Interests, Personal, Advisory Board, Consultancy/Advisory: Pfizer, Merck, Roche, BMS, Bayer, AstraZeneca, Astellas, Janssen, Seattle Genetics, Immunomedex. H.P. Gurney: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, MSD, Merck, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Merck; Financial Interests, Personal, Other, DSMB: AGITG. J. Bedke: Financial Interests, Institutional, Funding, Institutional Payment for Study funding: Eisai, Ipsen, MSD, Novartis, Roche, Pfizer; Financial Interests, Institutional, Other, Consulting fees: MSD, BMS, Pfizer; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, BMS, Eisai, Ipsen, MSD, Novartis, Roche, EUSA Pharma, Nektar, Pfizer. M.S. van der Heijden: Financial Interests, Institutional, Research Grant: BMS Roche AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS, Roche, AstraZeneca, Janssen, Seagen. M. Campbell: Financial Interests, Personal, Stocks/Shares: Seagen Inc.; Financial Interests, Personal, Other, Employee: Seagen Inc. D.P. Petrylak: Financial Interests, Institutional, Research Grant: Ada Cap (Advanced Accelerator Applications), Agensys Inc, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer; Financial Interests, Personal, Stocks/Shares: Bellicum (Sold 7/2020), Tyme (sold 10/2019); Financial Interests, Personal, Other, Consultant Fees: Ada Cap (Advanced Accelerator Applications) Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Incyte, Janssen, Mirati, Monopteros, Pfizer, Pharmacyclics, Roche, Seagen. All other authors have declared no conflicts of interest.