1972P - Pre-treatment (Tx) risk factors for enfortumab vedotin-induced peripheral neuropathy (EVIPN) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of UNITE

Background

PN is a debilitating and frequent dose-limiting toxicity of EV in pts with aUC. Knowledge on pt-specific risk factors for EVIPN is limited. We hypothesized certain pre-Tx clinical factors would be associated with increased risk for EVIPN.

Methods

UNITE is a multi-site retrospective study of EV-treated pts with aUC. EV monotherapy-treated pts with available clinical data and EV toxicities assessed per CTCAE v5.0 were analyzed. Associations between a priori selected clinical factors at EV start and EVIPN development were assessed in univariable analyses (UVA) using logistic regression and in separate multivariable logistic regression (MVA) models to adjust for confounding factors.

Results

Among 485 pts at 17 US sites, 176 developed any-grade EVIPN vs 309 who did not. At EV start: median (med) age 71; 339 (70%) men; 428 (88%) White; 366 (75%) ECOG PS 0-1; 90 (19%) prior diabetes (DM); 178 (37%) prior neuropathy (N); 325 (67%) had ≥2 Tx lines including 300 (62%) any prior platinum (PBC), 361 (74%) checkpoint inhibitor (CPI) preceding EV. Med BMI 26 kg/m², albumin (A) 3.7 g/dL, GFR 53 mL/min. Med f/up from EV start 9.1 mo (95% CI 8.4-10.3); time on EV 4.1 mo [IQR 1.4, 6.7]; time from EV start to EVIPN onset 2.5 mo [IQR 1.2, 4.6]. Most pts (156, 89%) had G1-2 EVIPN; 20 (11%) ≥G3; 45 (9% of all pts) discontinued EV due to EVIPN. In UVA, prior N, CPI preceding EV, higher A were associated with higher odds of EVIPN; prior DM, PBC with lower odds. In MVA, higher A, prior N were associated with increased risk for EVIPN; prior DM with decreased risk (all p

Conclusions

A MVA of EV-treated pts with aUC identified putative pre-Tx factors associated with higher risk for EVIPN. Our hypothesis-generating results suggest closer monitoring and earlier intervention to mitigate EVIPN may be warranted for certain pts starting EV, including those with higher A and prior N. Prospective studies to identify and validate risk factors for EVIPN are needed.

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. D.R. Bakaloudi: Financial Interests, Personal and Institutional, Research Funding: KureIt Cancer Research Award. 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. P.M. Coelho Barata: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Eisai, Exelixis, Janssen, EMD Serono, Pfizer, Seattle Genetics, BMS, Bayer; Financial Interests, Personal, Invited Speaker: Caris Life Sciences, Telix; Financial Interests, Personal, Other, educational videos: UroToday; Financial Interests, Institutional, Steering Committee Member: Exelixis, Telix; Financial Interests, Institutional, Local PI: Merck. Y. Zakharia: Financial Interests, Personal, Advisory Board: Pfizer, Eisai, Exelixis, Myovant, BMS, EMD Serono, Jannsen. M.I. Milowsky: Financial Interests, Personal, Other, Co-Editor-in-Chief, Clinical Genitourinary Cancer: Elsevier; Financial Interests, Personal, Invited Speaker: Medscape, Research to Practice; Financial Interests, Personal, Stocks/Shares: Pfizer, Merck, Gilead Sciences; Financial Interests, Institutional, Local PI: Merck, Roche/Genentech, Bristol Myers Squibb, Mirati Therapeutics, Seagen, G1 Therapeutics, 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, OncoC4, Flare Therapeutics, Loxo/Lilly; Non-Financial Interests, Advisory Role: G1 Therapeutics, Loxo/Lilly. D. Kilari: Financial Interests, Personal, Invited Speaker: Janssen, Pfizer, Aveo Oncology, Seagen, MJH - Life Sciences, Binayatra Foundation; Financial Interests, Personal, Advisory Board: Exelixis, Eisai; Financial Interests, Institutional, Coordinating PI: Exelixis, Genentech. 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. A.R. Khaki: Financial Interests, Institutional, Local PI: 23andMe, Janssen, Acrivon Therapeutics; Non-Financial Interests, Advisory Role, Consulting/advisory, declined compensation: Janssen. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Janssen, Aveo, Cardinal Health, Eisai, BMS. 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 Serono; 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. P. Grivas: Financial Interests, Personal, Advisory Role: MSD, Bristol Myers Squibb, AstraZeneca, EMD Serono, Seagen, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, BostonGene, Fresenius Kabi, Lucene Health, PureTech, G1 Therapeutics, Aadi Bioscences, CG Oncology, Strata Oncology, ImmunityBio, Asieris Pharmaceuticals, AbbVie; Financial Interests, Institutional, Research Funding: Pfizer, Bristol Myers Squibb, MSD, 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: AstraZeneca; 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. A.S. Alva: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck, Pfizer; Financial Interests, Personal, Other, Travel and Accommodation Expenses: Bristol Myers Squibb, Merck; Financial Interests, Institutional, Research Funding: Arcus Biosciences, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Genentech, MSD, Janssen, Mirati Therapeutics, Progenics, Prometheus Laboratories, Roche. 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. All other authors have declared no conflicts of interest.