1989P - Efficacy of enfortumab vedotin (EV) in patients (pts) with (w) advanced urothelial carcinoma (aUC) who have baseline neuropathy (N) and/or diabetes mellitus (DM): A UNITE study analysis

Background

EV is regulatory approved for aUC in combination w pembrolizumab and as monotherapy. Many pts w prior N and DM were excluded from landmark EV trials. We investigated real world outcomes on EV for pts w prior N and/or DM, hypothesizing no significant difference.

Methods

Pts treated w EV (combination + monotherapy) in the multi-site retrospective UNITE study were analyzed among 4 nonexclusive subgroups: baseline N, DM, N + DM, or neither. Kaplan-Meier method and Cox models evaluated duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Logistic regression evaluated observed response rate (ORR). Multivariate (MVA) models included age, sex, BMI, histology subtype (HS), ECOG performance, liver metastasis presence, and number of treatment lines as covariates.

Results

666 pts (17 sites) were evaluated w median age 70 yrs, 89% White, 71% men, median BMI 26, 27% upper tract primary, 36% variant HS component, 27% liver metastasis, 78% ECOG 0-1, and 13% received EV frontline. Baseline N, DM, and N + DM rates were 36%, 18% (5% insulin dependent), and 7%, respectively. In univariate Cox analysis, baseline N was associated w significantly longer PFS (HR 0.81 [95% CI 0.66-0.98], p = 0.031) but no significant OS difference (HR 0.86 [95% CI 0.69-1.08], p = 0.19). Baseline DM trended not significantly for PFS (HR 1.19 [95% CI 0.93-1.53], p = 0.16) or OS (HR 1.2 [95% CI 0.91-1.59], p = 0.2). MVA analysis showed significantly longer PFS (HR 0.76 [95% CI 0.62-0.92], p = 0.006) and OS (HR 0.78 [95% CI 0.62-0.98], p = 0.035) for pts w baseline N, w no significant differences noted for DM. Pts w N had significantly higher discontinuation (DC) rate due to EV intolerance compared to pts w no N/DM (p = 0.031). Table: 1989P

Conclusions

Pts w baseline N and/or DM do not appear to have inferior outcomes w EV, although DC rate was higher w baseline N. This supports EV treatment despite comorbidities w careful monitoring of N and DM toxicities.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Nizam: Financial Interests, Personal, Advisory Board, $1500 honorarium: Aveo Pharmaceuticals, Inc.; Financial Interests, Personal, Invited Speaker, $250 honorarium 2/2023: Cleveland Clinic Foundation; Financial Interests, Personal, Other, $600 honorarium 8/2023: Aptitude Health, Inc.; Financial Interests, Personal, Invited Speaker, $2000 honorarium. Tumor Board Tuesday Faculty 10/2023: IntegrityCE; Financial Interests, Personal, Other, Honorarium 8/2023: Targeted Oncology; Financial Interests, Personal, Invited Speaker, $1000 + travel expenses. Invited faculty for Winter Cancer Symposium 3/2024: MECC Global Meetings; Financial Interests, Personal, Advisory Board, Honorarium 1/2024: Pfizer/Seagen, Astellas Pharma; Financial Interests, Personal, Invited Speaker, Honorarium + travel expenses. Invited faculty for ASCO Advantage RCC 4/2024: ASCO; Financial Interests, Personal, Other, Section Editor for Advanced Urothelial Carcinoma; Honorarium 4/2024-10/2024: GU Oncology Now; Non-Financial Interests, Member: American Society of Clinical Oncology / Association for Clinical Oncology PAC. A.S. Alva: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, Pfizer, BMS; Financial Interests, Institutional, Research Funding: Genentech, Bristol Myers Squibb, Merck Sharp & Dohme, Prometheus, Mirati Therapeutics, AstraZeneca, Roche, Bayer, Astellas Pharma, Arcus Biosciences, Progenics, Celgene, Janssen. P. Grivas: Financial Interests, Personal, Advisory Role: Merck, Bristol Myers Squibb, AstraZeneca, EMD Serono, Seattle Genetics, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, BostonGene, Fresenius Kabi, Lucence Health, PureTech, G1 Therapeutics, Aadi Biosciences, CG Oncology, Strata Oncology, ImmunityBio, Asieris Pharmaceuticals, AbbVie; Financial Interests, Institutional, Research Funding: Pfizer, Bristol Myers Squibb, Merck, QED Therapeutics, GSK, Mirati Therapeutics, EMD Serono, G1 Therapeutics, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, Genentech. J. Bellmunt: Financial Interests, Personal, Advisory Board, Joined the Global adboard this year: Pfizer; Financial Interests, Personal, Advisory Board, Regular GU adboard for bladder cancer: Astra-Zeneca; Financial Interests, Personal, Invited Speaker, Lectures in the setting of National meetings: Merck; Financial Interests, Personal, Advisory Board, Bladder adboard: Merck; Financial Interests, Personal, Advisory Board, For the adjuvant study CM 247: BMS; Financial Interests, Personal, Invited Speaker, For ESMO Asia Symp 2020: MSD; Financial Interests, Personal, Stocks/Shares, Holdings: Bicycle; Financial Interests, Personal, Royalties, Role as Section Editor for Bladder: UpToDate; Financial Interests, Institutional, Coordinating PI, Pi of INDUCOMAIN Study (Avelumab first line in unfit patients) Though APRO Association: MSD; Financial Interests, Institutional, Coordinating PI, Pi of Prostate Study (Avelumab + Carboplatin) Though APRO Association: Pfizer; Non-Financial Interests, Other, Steering committee member of IMvigor 011: Genentech; Non-Financial Interests, Member: ASCO. C.J. Hoimes: Financial Interests, Personal, Advisory Board: Astellas, BMS, Foundation Medicine, Merck &Co, Seagen, Tempus, Adaptimmune; Financial Interests, Personal, Invited Speaker: BMS, Eisai; Financial Interests, Institutional, Advisory Board: Dynavax; Financial Interests, Institutional, Local PI: AbbVie, Alkermes, Astellas, BMS, Bayer, Bellicum, BioNTech, Dynavax, Genentech, Janssen, Mirati, NeoImmune Tech, Pfizer, Promontory, Tyra, Xencor, CRISPR; Financial Interests, Personal and Institutional, Steering Committee Member: Merck &Co, Seagen. M.A. Bilen: Financial Interests, Personal, Advisory Board: Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Nektar, EMD Serono, Seagen, Sanofi; Financial Interests, Institutional, Local PI: Merck, Xencor, Bayer, Bristol Myers Squibb, Genentech/Roche, Seagen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, Pfizer. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Janssen, Aveo, Cardinal Health, Eisai, BMS. M.I. Milowsky: Financial Interests, Personal, Stocks or ownership: Pfizer, Merck, Gilead Sciences; Financial Interests, Institutional, Research Funding: Merck, Bristol Myers Squibb, Mirati Therapeutics, Seagen, Alliance Foundation Trials, Alliance for Clinical Trials in Oncology, Clovis Oncology, Arvinas, ALX Oncology, Hoosier Cancer Research Network, Novartis, Acrivon Therapeutics, Astellas Pharma, Genentech, Accuray, PCCTC, G1 Therapeutics, OncoC4, Flare Therapeutics, Loxo/Lilly, Roche; Financial Interests, Personal, Other: Elsevier, Medscape, ResearchToPractice; Other, Personal, Other, Uncompensated Relationship: G1 Therapeutics, Loxo/Lilly. A.R. Khaki: Financial Interests, Institutional, Local PI: 23andMe, Janssen, Acrivon Therapeutics; Non-Financial Interests, Advisory Role, Consulting/advisory, declined compensation: Janssen. S. Gupta: Financial Interests, Personal, Advisory Board: Seattle Genetics, BMS, Pfizer, Bayer, Merck, Gilead, Loxo Oncology, Guardant, Foundation one; Financial Interests, Personal, Other, Speaker's Bureau: Janssen; Financial Interests, Personal, Other, Consultant: EMD Sorono; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Stocks/Shares: BioNTech, Moderna; Financial Interests, Personal, Steering Committee Member: BMS, Merck, Seattle Genetics, Acrivon; Financial Interests, Institutional, Local PI: EMD Sorono, Gilead, Roche, QED, Exelixis, Moderna, Pfizer. M.T. Campbell: Financial Interests, Personal, Advisory Board: Exelixis, Pfizer, Seagen, AstraZeneca, Curio Science, Eisai; Financial Interests, Personal, Invited Speaker: MJH Life Science, Dave Oncology; Financial Interests, Institutional, Local PI: Pfizer, Aravive, Seagen; Financial Interests, Institutional, Coordinating PI: Exelixis, Janssen, AstraZeneca; Financial Interests, Institutional, Funding: United States Department of Defense. O. Alhalabi: Financial Interests, Personal, Advisory Board: Seagen, Silverback therapeutics, Cardinal health, Adaptimmune, Bicycle Therapeutics; Financial Interests, Personal, Invited Speaker: Curio Science; Financial Interests, Institutional, Local PI: Ikena Oncology, Arcus Biosciences, AstraZeneca, Roche Genentech. V.S. Koshkin: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Pfizer, EMD Serono; Financial Interests, Personal, Other, Consulting: GLG, ExpertConnect, Guidepoint; Financial Interests, Personal, Advisory Board, Advisory Board Participation: MSD, Bicycle Therapeutics; Financial Interests, Institutional, Local PI: Merck, Taiho, Eli Lilly, Clovis, Novartis, Nektar, Curium, Gilead; Financial Interests, Institutional, Steering Committee Member: Seagen; Financial Interests, Personal and Institutional, Research Grant: Prostate Cancer Foundation. J.R. Brown: Financial Interests, Personal, Invited Speaker, Speaker's Bureau for Avelumab: EMD Serono; Financial Interests, Personal, Invited Speaker, Speaker for MSL Training: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, EMD Serono, Janssen/Johnson & Johnson; Financial Interests, Institutional, Local PI: Pfizer, Bicycle Therapeutics, Roche. All other authors have declared no conflicts of interest.