Antibody-drug Conjugates in  The Management of Advanced Urothelial Carcinoma

Pooya Dibajnia; Aly-Khan Lalani

doi:10.58931/cot.2024.1329

Authors

Pooya Dibajnia, BSc (Hons), MD, FRCPC Juravinski Cancer Centre, McMaster University, Hamilton, ON
Aly-Khan Lalani, BSc (Hons), MD, FRCPC Juravinski Cancer Centre, McMaster University, Hamilton, ON

DOI:

https://doi.org/10.58931/cot.2024.1329

Abstract

For decades, the cornerstone for treatment of advanced urothelial carcinoma (aUC) has consisted of platinum-based chemotherapy regimens, such as GC (gemcitabine plus cisplatin/carboplatin) or MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin). Thereafter, immune checkpoint inhibitors (ICI) were incorporated into the standard of care, initially as monotherapy in subsequent-line settings and more recently as maintenance treatment with chemotherapy in the first-line setting. Recently, the development of antibody-drug conjugates (ADCs) has dramatically shifted the treatment landscape for aUC.

ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities.

ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities.

Author Biographies

Pooya Dibajnia, BSc (Hons), MD, FRCPC, Juravinski Cancer Centre, McMaster University, Hamilton, ON

Dr. Pooya Dibajnia is a Genitourinary Oncology fellow at the Juravinski Cancer Centre, McMaster University, Hamilton, Ontario. He completed his medical degree at University of Toronto, internal medicine residency at NOSM University, and medical oncology sub-specialty residency at McMaster University. His clinical interests are in renal cell carcinoma and urothelial carcinoma. His research interests focus on real-world evidence, and he has recently presented his work at the ASCO 2024 meeting.

Aly-Khan Lalani, BSc (Hons), MD, FRCPC, Juravinski Cancer Centre, McMaster University, Hamilton, ON

Dr. Lalani is an Associate Professor at McMaster University and a Medical Oncologist at the Juravinski Cancer Centre (JCC). He is the Chair for the Genitourinary (GU) Cancers Disease Site Team at the JCC. His academic interests include clinical trial design and translational work for GU malignancies. He is a Scientist with the Escarpment Cancer Research Institute, and an Associate Member of the Centre for Discovery in Cancer Research at McMaster University. He is also co-host of the podcast “The View on GU”. Aly-Khan was awarded the Elizabeth Eisenhauer Early Drug Development Young Investigator Award from the Canadian Cancer Trials Group in 2022; and the Rising Star Award from the Canadian Association of Medical Oncologists in 2023.

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Antibody-drug Conjugates in The Management of Advanced Urothelial Carcinoma

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Author Biographies

Pooya Dibajnia, BSc (Hons), MD, FRCPC, Juravinski Cancer Centre, McMaster University, Hamilton, ON

Aly-Khan Lalani, BSc (Hons), MD, FRCPC, Juravinski Cancer Centre, McMaster University, Hamilton, ON

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