Antibody-drug conjugates in urothelial carcinoma: current status and future
Samuel Ruder1, Juana Martinez2, Jessica Palmer1
1Department of Medicine, Division of Hematology and Oncology, New York Presbyterian Weill Cornell Medical Center.
Purpose Of Review:
Antibody-drug conjugates (ADCs) are quickly becoming frontline standard of care in many tumor types, including urothelial carcinoma. This review summarizes recent clinical investigations into the use of ADCs targeting nectin-4, trophoblast cell surface antigen-2 (Trop-2), human epidermal growth factor receptor 2 (HER-2), and other antigens in urothelial carcinoma.
Recent Findings:
This review covers efficacy and toxicity data of ADCs alone and in combination with immunotherapy; mechanisms of resistance; and preclinical studies that provide biological basis for clinical approaches.
Summary:
Enfortumab vedotin and sacituzumab govitecan can be used in an unselected group of patients with urothelial carcinoma whereas HER-2 ADCs have only been administered in those with high expression or amplification. Most are being studied in combination with immune checkpoint inhibitors. Data supports use of enfortumab vedotin in combination with pembrolizumab as first-line therapy in metastatic/unresectable locally advanced urothelial carcinoma. Sacituzumab govitecan may be used as later-line option in these patients. HER-2 therapy is still under investigation but has many recent promising results.
Insights
Antibody-drug conjugates (ADCs) targeting nectin-4, Trop-2, and HER-2 are advancing urothelial carcinoma treatment. Enfortumab vedotin and sacituzumab govitecan show promise, with HER-2 ADCs under investigation.
Area of Science:
- Oncology
- Pharmacology
Background:
- Antibody-drug conjugates (ADCs) are increasingly vital in treating various cancers, including urothelial carcinoma.
- Several ADCs targeting specific antigens are under clinical investigation for urothelial carcinoma.
Purpose of the Study:
- To review recent clinical investigations of ADCs targeting nectin-4, Trop-2, HER-2, and other antigens in urothelial carcinoma.
- To summarize efficacy, toxicity, resistance mechanisms, and preclinical data for these ADCs.
Main Methods:
- Literature review of clinical trials and preclinical studies on ADCs in urothelial carcinoma.
- Analysis of efficacy and toxicity data for ADCs alone and in combination with immunotherapy.
Main Results:
- Enfortumab vedotin and sacituzumab govitecan are effective in unselected urothelial carcinoma patients.
- HER-2 ADCs show promise but are limited to patients with high HER-2 expression/amplification.
- Combination therapies, particularly with immune checkpoint inhibitors, are under active investigation.
Conclusions:
- Enfortumab vedotin plus pembrolizumab is supported as first-line therapy for metastatic/unresectable locally advanced urothelial carcinoma.
- Sacituzumab govitecan serves as a later-line option.
- HER-2 targeted ADC therapy is promising and warrants further investigation.
More Related Videos
07:36Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
11:02Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:31Hybridoma Technology
Hybridoma Selection
Commonly used fusion techniques — electroporation,...