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Defining Clinical Endpoints in Castration-Resistant Prostate Cancer

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Management of Castration Resistant Prostate Cancer

Part of the book series: Current Clinical Urology ((CCU))

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Abstract

Over the past five years a better understanding of the biology of CRPC has led to the regulatory approval of five new agents, all having evidence of the ability to improve overall survival (OS). The introduction of these novel compounds in our treatment armamentarium will likely challenge future drug development and registration strategies for new agents undergoing clinical testing in this patient population. The utility of endpoints including prostate-specific antigen (PSA), progression-free survival (PFS), and overall response rate (ORR) used in clinical trial development are now challenged by the apparent disconnect between OS, and these commonly used intermediate markers of clinical efficacy. Quality of life (QOL), pain, and skeletal-related complications have also become attractive potential endpoints for drug development given the bone tropism of metastatic prostate cancer. Drug development both in the pre- and post-chemotherapy settings will be faced with new levels of complexity as many of the novel agents recently approved are used earlier in the management of the disease. Similarly, recent data suggesting that earlier use of chemotherapy for men with metastatic hormone-naïve prostate cancer, i.e. given concomitantly with androgen deprivation therapy (ADT) leads to improved survival will also challenge future trial design in men with castration-responsive disease. In this chapter, we review traditional endpoints used for drug development in mCRPC and discuss some of the challenges faced when interpreting clinical drug development in this setting.

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Authors and Affiliations

  1. Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue/R35, Cleveland, OH, 44195, USA

    Jorge A. Garcia MD, FACP & Robert Dreicer MD

  2. Department of Urology, Cleveland Clinic Glickman Urological and Kidney Institute, 9500 Euclid Avenue/R35, Cleveland, OH, 44195, USA

    Jorge A. Garcia MD, FACP & Robert Dreicer MD

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  1. Jorge A. Garcia MD, FACP
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  2. Robert Dreicer MD
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Correspondence to Jorge A. Garcia MD, FACP .

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Editors and Affiliations

  1. Department of Surgery, University of Montreal Hospital Center, Montreal, Québec, Canada

    Fred Saad

  2. Department of Oncology, The Johns Hopkins University, Baltimore, Maryland, USA

    Mario A. Eisenberger

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Garcia, J.A., Dreicer, R. (2014). Defining Clinical Endpoints in Castration-Resistant Prostate Cancer. In: Saad, F., Eisenberger, M. (eds) Management of Castration Resistant Prostate Cancer. Current Clinical Urology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1176-9_14

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