Emerging monoclonal antibody therapies in the treatment of metastatic urothelial carcinoma

ABSTRACT

Introduction

The treatment landscape for advanced-stage, unresectable or metastatic urothelial carcinoma (mUC) has shifted dramatically over a short period of time, with new therapeutic agents available for clinical use. However, despite these recent advances in the field, mUC continues to be a disease with significant morbidity and mortality and remains generally incurable. While platinum-based therapy remains the backbone of therapy, many patients are ineligible for chemotherapy or have failed initial chemotherapy treatment. In post-platinum treated patients, immunotherapy and antibody drug conjugates have provided incremental advances, but agents with better therapeutic index guided by precision medicine are needed.

Areas covered

This article covers the available monoclonal antibody therapies in mUC excluding immunotherapy and antibody drug conjugates. Included are a review of data utilizing monoclonal antibodies targeting VEG-F, HER-2, FGFR, and KIR-2 in the setting of mUC. A literature search from 6/2022– 9/2022 was performed utilizing PubMed with key terms including urothelial carcinoma, monoclonal antibody, VEG-F, HER-2, FGFR.

Expert opinion

Often used in combination with immunotherapy or other therapeutic agents, monoclonal antibody therapies have exhibited efficacy in mUC in early trials. Upcoming clinical trials will further explore their full clinical utility in treating mUC patients.

KEYWORDS:

• Monoclonal antibody therapy
• urothelial carcinoma
• VEG-F
• HER-2
• FGFR
• KIR-2

Article highlights

• Brief review of current treatments for metastatic urothelial carcinoma with in depth review of monoclonal antibody treatments.

• Treatments targeting VEGF, HER-2, FGFR are highlighted.

• Future directions with ongoing clinical trials for monoclonal antibody therapies are highlighted.

• Expert opinion regarding the current state and future directions of monoclonal antibody therapy for urothelial carcinoma is emphasized.

Declaration of interests

R Jain reports being on the Advisory Board of Seattle Genetics, Gilead, Aveo, BMS and on the Speakers Bureau for Seattle Genetics, and Gilead. They have been a consultant/Scientific Review Committee Member for NCCN. They have received research support to their institution from BMS, Gilead, and NCI, as well as an Honorarium from Dava Oncology.

G. Sonpavde reports being on the Advisory Board of EMD Serono, BMS, Merck, Seattle Genetics/Astellas, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Lucence Health, IMV, and Vial. They also report being a consultant or on the Scientific Advisory Board (SAB) for Suba Therapeutics and Syapse. They have received research support to their institution from Sanofi, Astrazeneca, Gilead, Helsinn, Lucence, EMD Serono, Jazz Therapeutics, Genecentric. They have received speaker and travel costs from BIO – INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, Seagen, Gilead, Natera, Exelixis. They are on the data safety monitoring committee (honorarium) for Mereo. G Sonpavde's spouse is employed by Myriad. They have received writing/editor fees from Uptodate, Editor of Elsevier Practice Update Bladder Cancer Center of Excellence.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.