Dataset Information

Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma.

ABSTRACT:

Introduction

Nectin-4 is a tumor-associated antigen overexpressed in urothelial carcinoma and several other malignancies. It has emerged as a compelling target for novel tumor-directed therapies, particularly as a component of antibody-drug conjugates (ADCs), a growing class of anti-cancer therapeutic agents. Development of nectin-4-directed therapies has been led by enfortumab vedotin (EV), an ADC comprised of a fully human monoclonal antibody specific for nectin-4 conjugated via a cleavable linker to the microtubule inhibitor MMAE. EV was approved in 2019 as a first-in-class agent for the treatment of urothelial carcinoma.

Areas covered

This article discusses general principles relevant to ADC design and our current understanding of nectin-4 in normal physiology and malignancy, followed by a review of the development of EV as well as additional drug conjugate strategies targeting nectin-4.

Expert opinion

EV offers proof-of-concept for the clinical utility of nectin-4-directed therapies and provides further support for ADCs as an important class of anti-cancer agents. Future development of nectin-4-targeted approaches will benefit from a deeper understanding of nectin-4 biology in both health and disease, as well as a detailed exploration of the mechanisms underlying therapeutic activity and resistance.

SUBMITTER: Wong JL

PROVIDER: S-EPMC8224177 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma.

Wong Jeffrey L JL Rosenberg Jonathan E JE

Expert opinion on biological therapy 20210524 7

<h4>Introduction</h4>Nectin-4 is a tumor-associated antigen overexpressed in urothelial carcinoma and several other malignancies. It has emerged as a compelling target for novel tumor-directed therapies, particularly as a component of antibody-drug conjugates (ADCs), a growing class of anti-cancer therapeutic agents. Development of nectin-4-directed therapies has been led by enfortumab vedotin (EV), an ADC comprised of a fully human monoclonal antibody specific for nectin-4 conjugated via a clea ...[more]

PMID: 34030536

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Project description:Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.

Dataset Information

Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma.

Introduction

Areas covered

Expert opinion

Publications

Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma.

Similar Datasets

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