A Molecular Inquiry into the Role of Antibody-Drug Conjugates in Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer

Woonyoung Choi; Kara Lombardo; Sunil Patel; Gabriel Epstein; Mingxiao Feng; Andrew Gabrielson; Noah M Hahn; Jean Hoffman-Censits; David McConkey; Trinity J Bivalacqua; Andres Matoso; Max Kates

doi:10.1016/j.eururo.2021.10.009

A Molecular Inquiry into the Role of Antibody-Drug Conjugates in Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer

Eur Urol. 2022 Feb;81(2):138-142. doi: 10.1016/j.eururo.2021.10.009. Epub 2021 Nov 1.

Authors

Affiliations

¹ Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
² Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
³ Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁴ Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁵ Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁶ Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: mkates@jhmi.edu.

PMID: 34736796
DOI: 10.1016/j.eururo.2021.10.009

Abstract

The treatment landscape for advanced urothelial cancer has changed dramatically owing to the US Food and Drug Administration approval and introduction of antibody-drug conjugates (ADCs), including enfortumab vedotin and sacituzumab govitecan. Efforts have begun to use these therapies in earlier disease states, specifically bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). We assessed gene expression associated with these newly approved therapies in a novel cohort of treatment-naïve NMIBC tumors before and after BCG therapy. Multiple genes, including Nectin-4, Trop-2, and Her-2, exhibited increased expression after BCG therapy compared to baseline. However, few of the tumors with increased expression of ADC targets also exhibited increased PD-L1/PD-1 expression. Taken together, these data demonstrate the heterogeneous genomic landscape of BCG-exposed NMIBC, and provide evidence supporting the evaluation of ADCs in NMIBC. PATIENT SUMMARY: We evaluated the potential role of targeted therapies that have been approved in the USA for advanced non-muscle-invasive bladder cancer (NMIBC) that has recurred after treatment with bacillus Calmette-Guérin (BCG). By assessing levels of specific genes and proteins linked to the targeted therapies, we demonstrate that there is rationale for further evaluation of these therapies in NMIBC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Administration, Intravesical
BCG Vaccine / therapeutic use
Female
Humans
Immunoconjugates* / therapeutic use
Male
Neoplasm Invasiveness
Neoplasm Recurrence, Local / pathology
Urinary Bladder Neoplasms* / drug therapy
Urinary Bladder Neoplasms* / genetics
Urinary Bladder Neoplasms* / pathology

Substances

Adjuvants, Immunologic
BCG Vaccine
Immunoconjugates