Future Strategies Involving Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma
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Genitourinary Cancers (S Gupta, Section Editor)
Future Strategies Involving Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma Guillaume Grisay, MD Julien Pierrard, MD Caterina Confente, MD Emmanuel Seront, MD, PhD* Address * Department of Medical Oncology, Hôpital de Jolimont, La Louvière, Belgium Email: [email protected]
* Springer Science+Business Media, LLC, part of Springer Nature 2020
This article is part of the Topical Collection on Genitourinary Cancers Keywords Urothelial carcinoma I Immune checkpoint inhibitors I Targeted therapy I Combination therapy I Anti-angiogenic agents I Biomarkers
Opinion statement Immune checkpoint inhibitors have importantly improved the outcome of patients with urothelial carcinoma. Different immune checkpoint inhibitors are currently approved and used in first- and second-line setting. The multiple agents currently approved in these setting make the choice sometimes difficult for clinicians. Furthermore, only a minority of patients present drastic response and long-term benefit with current immunotherapy. In this review, we describe the current use of immunotherapy in urothelial carcinoma but we also highlight the new strategies of treatment involving immune checkpoint inhibitors; we describe the place of immunotherapy with chemotherapy, targeted agents, and antiangiogenic agents, incorporating the recent results presented at ASCO 2020. This review explores also the different action mechanisms of immune checkpoint inhibitors and the molecular rational to evaluate these agents in other strategies, such as maintenance and salvage strategies. The new advances in biomarker development are also presented.
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Curr. Treat. Options in Oncol.
(2021) 22:7
Introduction Urinary tract cancer is the ninth most common malignancy in the world, with an annual incidence of almost 275,000 new cases worldwide and an estimated 165,000 deaths each year [1–4]. Urothelial carcinoma (UC), also known as transitional cell carcinoma, accounts for 90% of all histologies; less frequent types are represented by squamous cell carcinoma, adenocarcinoma, and small cell carcinoma [5]. UC develops mainly in bladder but can also arise from other sites in the urinary tract such as the kidney, ureter, and urethra. Seventy percent of patients with bladder cancer present “superficial” or non-muscle invasive bladder cancer (NMIBC) and are treated with a curative intent. Conversely, muscle-invasive UC (MIUC) is an aggressive disease that requires multimodality therapy including cystectomy and chemotherapy. Despite aggressive management, around 50% of patients with MIUC will develop metastases with an estimated median survival of 14 months [6]. In metastatic setting, standard treatment in fit and cisplatin-eligible patients consists in platinum-
based therapies, such as gemcitabine and cisplatin (GC) or methotrexate, vinblastine, adriamycin, cisplatin (MVAC), and results in an overall response rates (ORR) ranging from 40 to 70%, a median progressionfree survival (PFS) of appro
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