Abstract 1775P
Background
Programmed death-ligand 1 (PD-L1) expression in aUC has been studied extensively in clinical trials. In the DANUBE trial, 60% of patients (pts) with aUC had high tumor PD-L1 expression using the Ventana PD-L1 (SP263) Assay. As the first-line (1L) aUC therapy landscape keeps evolving, discovery and validation of biomarkers with the clinical utility to enable patient selection is important. In that context, there is a need to better understand testing practices and the prevalence of PD-L1 for patients with aUC in the real-world setting.
Methods
PREVAIL (NCT03788746) enrolled pts with locally advanced/metastatic UC undergoing 1L therapy at community practice sites who had pre-treatment tumor tissue available for central PD-L1 testing with the Ventana PD-L1 (SP263) Assay. The primary endpoint was the prevalence of pre-treatment tumor PD-L1 high expression, defined as ≥25% of tumor cells (TCs) exhibiting membranous staining or, immune cells present (ICP) >1% and immune cells with staining (IC+) ≥25% or, ICP=1% and IC+ =100%.
Results
Among 129 evaluable pts (median age, 72 yrs; 66% men; 86% White; 25% upper tract tumor; 85% ECOG PS 0-1; 35% visceral metastases; 25% never smokers), pre-treatment PD-L1 expression was high in 71 (55%) pts (Table). Prior to entry into the PREVAIL study, only 33 (26%) patients had prior PD-L1 testing. Table: 1775P
Pre-treatment PD-L1 expression status
| PD-L1 status | PREVAIL (Ventana SP263 Assay) (n=129) | Prior PD-L1 testing | |
| Dako IHC 22C3 (n=24) | Other (n=9) | ||
| High | 71 (55%) | 14 (58%) | 5 (56%) |
| Low | 58 (45%) | 10 (42%) | 4 (44%) |
Conclusions
The prevalence of PD-L1 high expression was 55% in the real-world community setting in patients who started 1L therapy for aUC, consistent with clinical trial data (eg, DANUBE, Javelin Bladder 100). Only a quarter of patients had prior PD-L1 testing, which limited inter-assay concordance evaluation. Additional baseline biomarkers - ie, tumor mutational burden (in tissue and plasma), ctDNA, genomic alterations - and their associations with 1L therapy response and clinical outcomes will be evaluated as data matures.
Clinical trial identification
NCT03788746.
Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice guidelines, was provided by Anne Jacobson, MSPharm, of CPD Content Group, LLC, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
P. Grivas: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, Bristol Myers Squibb, Clovis Oncology, EMD Serono, Seattle Genetics, Pfizer, Janssen, Genzyme, Mirati Therapeutics, Exelixis, Genentech/Roche, GlaxoSmithKline, Immunomedics, Dyania Health, Infinity Pharmaceuticals, QED Therapeutics, 4D Pharma PLC; Financial Interests, Personal, Other, consulting: Foundation Medicine; Financial Interests, Institutional, Invited Speaker: Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics, Bristol Myers Squibb, Debiopharm Group, Merck, QED Therapeutics, GlaxoSmithKline, Mirati Therapeutics. P.K. Agarwal: Financial Interests, Advisory Role: AstraZeneca, AURA, Verity, UroGen, Janssen. H. Al-Ahmadie: Financial Interests, Advisory Role: AstraZeneca, Janssen Biotech, Paige. T. Friedlander: Financial Interests, Research Grant: Seagen, Roche Genentech; Financial Interests, Advisory Role: Taiho, EMD Serono, AbbVie, Foundation Medicine, Astellas, Basilea Oncology. D. Geynisman: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Exelixis, Astellas, Genentech; Financial Interests, Institutional, Invited Speaker: Genentech, Merck, Harpoon, Seattle Genetics. I. Hussain: Financial Interests, Full or part-time Employment: AstraZeneca. Y. Lotan: Financial Interests, Advisory Role: Nanorobotics, C2I genomics, Photocure, AstraZeneca, Merck, Fergene, AbbVie, Cleveland Diagnostics, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, verity pharmaceuticals, virtuoso surgical, Nanorobot, Stimit, Urogen, Vessi, CAPs medical, Xcures, BMS, Aura Biosciences, Inc. A.K. Morgans: Financial Interests, Advisory Role: Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Novartis, Pfizer, Sanofi. M. Tesic-Schnell: Financial Interests, Full or part-time Employment: AstraZeneca. J. Meeks: Financial Interests, Advisory Role: AstraZeneca, Merck, UroGen, BMS, Janssen, Prokarium; Financial Interests, Invited Speaker: Olympus.