Treatment options for advanced urothelial cancer after progression on chemotherapy and immune checkpoint inhibitors: a literature review.

OBJECTIVE

To describe the current treatment landscape in advanced urothelial cancer (aUC)/metastatic urothelial cancer and in particular to review the relevant literature highlighting recent advances in the treatment of patients with aUC after progression on chemotherapy and immune checkpoint inhibitor (ICI).

BACKGROUND

aUC is a very aggressive disease with poor outcomes. Over the past several years, its treatment landscape has seen significant advances with the approval of ICI and targeted agents, which have led to improved outcomes. The current standard of care for most patients with aUC involves platinum-based chemotherapy followed by ICI after progression or as switch maintenance therapy (if no progression after chemotherapy). Treatment of patients following progression on ICI is more challenging, but novel therapies have been approved, such as erdafitinib for tumors with fibroblast growth factor receptor 2 (FGFR2) or FGFR3 activating mutation or fusion (can also be used following progression on platinum-based chemotherapy), enfortumab vedotin (EV) and sacituzumab govitecan (SG) in an unselected patient population. Many other trials in this space are currently ongoing and other promising agents may also potentially become available in the future.

METHODS

Narrative overview of the recent literature relevant to the treatment of advanced/metastatic urothelial cancer following progression on chemotherapy and ICI was undertaken. Relevant literature was obtained from review of computerized databases including pubmed.gov and proceedings of major conferences including American Society of clinical Oncology (ASCO) Meetings, GU ASCO Symposia and European Society of Medical Oncology (ESMO) Meetings.

CONCLUSIONS

In this narrative review, we highlight the current dynamic treatment landscape in aUC, emphasizing the recent important developments and a few examples of ongoing clinical trials. In particular, we focus on therapy options available following progression on platinum-based chemotherapy and ICI, a treatment space where until recently there had been no FDA-approved treatment options. The recent pivotal trials of antibody drug conjugates (ADCs) that led to FDA approvals in this space are highlighted, as are other agents currently in development. We conclude by discussing future directions and ongoing challenges in this evolving disease space.

Informations de copyright

2021 Translational Andrology and Urology. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-21-123). The series “Management of Advanced Genitourinary Malignancies” was commissioned by the editorial office without any funding or sponsorship. Dr. PG serves as an unpaid editorial board member of Translational Andrology and Urology from Jul 2018 to Jun 2020. Dr. VSK reports outside funding for the institution from Nektar, Janssen, Clovis, and Endocyte, personal fees from Pfizer, Janssen, AstraZeneca, Dendreon, Clovis, and Seattle Genetics/Astellas, outside the submitted work. In the last 3 years (unrelated to this manuscript), Dr. PG has provided consulting to AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Heron Therapeutics, Immunomedics/Gilead, Infinity Pharmaceuticals, Janssen, Merck & Co., Mirati Therapeutics, Pfizer, Regeneron Pharmaceuticals, QED Therapeutics, Seattle Genetics, 4D Pharma PLC; his institution has received research funding from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck & Co., Mirati Therapeutics, Pfizer, QED Therapeutics. Dr. ASO has no other conflicts of interest to declare.