1988P - Enfortumab vedotin (EV) + pembrolizumab (P) outcomes outside clinical trials and biomarkers of benefit in patients (pts) with advanced urothelial carcinoma: Analysis of the UNITE study

Background

First-line (1L) EV/P demonstrated improved outcomes vs platinum-based chemotherapy in EV-302 trial. Data on outcomes outside clinical trials (CT) and biomarkers associated with EV/P treatment benefit are lacking.

Methods

Pts treated with EV/P were identified in the multi-site, retrospective UNITE study. Observed response rate (ORR) was assessed in evaluable pts (imaging after ≥1 EV/P cycle) treated outside CT. Biomarkers were assessed in all pts with available data, including genomic alterations (alts) from next-generation sequencing (NGS) present in ≥10% of pts. Each individual biomarker was evaluated in univariate analyses (UVA), followed by separate multivariate analyses (MVA) to account for clinical variables. ORR was assessed using logistic regression; progression-free survival (PFS) and overall survival (OS) from EV/P start using the log-rank test and cox proportional hazard modeling.

Results

Among 189 pts treated with EV/P at 14 US sites, 171 received treatment outside CT, and 118 had NGS data available. Median age was 71; 139 (74%) men, 159 (84%) Caucasian, 140 (74%) with ECOG PS 0/1, 119 (63%) with pure urothelial histology and 31 (16%) with liver mets. Outcomes with EV/P are noted in the Table. For pts with NGS data, in the UVA, longer PFS and OS were associated with ECOG PS 0/1, albumin ≥ 3.5mg/dL, NLR ≥ 5, Hgb ≥10g/dL, while shorter OS and PFS with TP53 and TERT alts. In MVA models, including these clinical variables along with age, race, and histology as covariates, shorter PFS was associated with alts in KMT2D [HR: 2.2 (95% CI: 1.0 – 4.5, p = 0.04] and TP53 [HR: 2.3 (95% CI: 1.2 – 4.2, p

Conclusions

In this multi-site retrospective cohort study with early follow-up, EV/P treatment outside CT showed robust DCR but a more modest ORR relative to outcomes from 1L CT. TP53 and KMT2D alts correlated with inferior EV/P outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

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. 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. 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. 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. 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 Serono, Gilead, Roche, QED, Exelixis, Moderna, Pfizer. 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. A. Basu: Financial Interests, Personal, Invited Speaker: Eisai, Natera; Financial Interests, Personal, Advisory Board: eisai, emd serono, aveo; Financial Interests, Personal, Stocks/Shares: Immunitybio; Financial Interests, Personal and Institutional, Coordinating PI: Roche; Financial Interests, Institutional, Local PI: merck; Financial Interests, Local PI: Aveo. 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.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. 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. A.S. Alva: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, Pfizer; 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. 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.