The Evolving Systemic Treatment Landscape for Patients with Advanced Prostate Cancer
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REVIEW ARTICLE
The Evolving Systemic Treatment Landscape for Patients with Advanced Prostate Cancer Martina Pagliuca1 · Carlo Buonerba1,2 · Karim Fizazi3 · Giuseppe Di Lorenzo1,4
© Springer Nature Switzerland AG 2019
Abstract Prostate cancer (PC) is a major health issue in developed countries, with, on the one hand, men suffering from sequelae related to unnecessary treatment of non-lethal PC, and, on the other hand, still dying because of advanced PC that progresses to castrationresistant disease. Systemic treatment is the mainstay of therapy of castration-resistant PC (CRPC). To date, a multitude of systemic agents have been tested and many of these have failed to provide a clinically meaningful benefit in CRPC, while others have been approved by the US Food and Drug Administration and/or the European Medicines Agency, including antiandrogen hormonal drugs (abiraterone, enzalutamide, apalutamide), chemotherapy (docetaxel and cabazitaxel), immunotherapy (Sipuleucel-T), and radiopharmaceutical (Radium-223) agents. In this review, systemic treatments regarded as most likely to have an impact in clinical practice are presented and discussed. In addition to the pivotal clinical studies, selected retrospective and non-randomized clinical trials are also discussed if deemed to have an impact on clinical practice or future research. A comprehensive appraisal of the expanding landscape of systemic therapies for advanced PC is provided from an expert perspective, with a focus on novel classification and diagnostic tools that have been paving the way for the development of precision medicine in PC. Key Points Some recent key advances in the systemic treatment of prostate cancer (PC) have been achieved by expanding the settings of use of already approved drugs, such as abiraterone and docetaxel in the castration-sensitive setting and enzalutamide in non-metastatic castration-resistant disease. While many targeted agents tested in advanced PC have failed, novel agents such as poly (ADP-ribose) polymerase inhibitors, prostate-specific membrane antigen-targeted radiopharmaceuticals, and immune checkpoint inhibitors hold great potential in selected patient populations. Martina Pagliuca and Carlo Buonerba contributed equally to this manuscript. * Giuseppe Di Lorenzo [email protected] 1
Department of Clinical Medicine and Surgery, University Federico II of Naples, Via Pansini 5, 80131 Naples, Italy
2
Experimental Zoo-prophylactic Institute of Southern Italy, Portici, Italy
3
Institut Gustave Roussy, University of Paris Sud, Villejuif, France
4
Department of Medicine, Università degli Studi del Molise, Campobasso, Italy
1 Introduction Prostate cancer (PC) represents approximately one in five new cancer diagnoses in men, with 164,649 new cases and 29,430 deaths estimated in the US in 2018. While patients with localized PC at diagnosis have a 5-year overall survival (OS) rate close to 100% [1], approximately one-third [2] experience disease recurrence/progression after their initial therapy and ultimately
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