Novel therapies are changing treatment paradigms in metastatic prostate cancer
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REVIEW
Novel therapies are changing treatment paradigms in metastatic prostate cancer Eric Powers1, Georgia Sofia Karachaliou2,3, Chester Kao1, Michael R. Harrison2,3, Christopher J. Hoimes2,3, Daniel J. George2,3, Andrew J. Armstrong2,3,4 and Tian Zhang2,3*
Abstract Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials. Keywords: Metastatic prostate cancer, Castration-resistant prostate cancer, Prostate-specific membrane antigen (PSMA), Polyadenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitor, Androgen receptor inhibitors (ARIs) Introduction Prostate cancer (PC) is the second most commonly diagnosed cancer among men worldwide, following lung cancer, and the first among men in the USA [1]. Although clinical outcomes are excellent for patients with localized disease, patients with metastatic prostate cancer (mPC) have poor prognosis, with a 5-year survival rate reaching 30%. Androgen deprivation therapy (ADT) has long been the treatment of choice as backbone of all other therapies, by reducing circulating androgens to castration levels and slowing the progression of the disease. Unfortunately, ADT as a single agent does not always prevent disease progression, and eventually hormone-sensitive prostate cancer (HSPC) will develop resistance even at low testosterone levels and become castration-resistant prostate cancer (CRPC).
*Correspondence: [email protected] 2 Division of Medical Oncology, Department of Medicine, Duke University, DUMC 103861, Durham, NC 27710, USA Full list of author information is available at the end of the article
Over the last few years, several successful phase-3 trials have expanded the available treatments in metastatic HSPC with docetaxel (CHAARTED, GETUG-AFU 15, and STAMPEDE [2, 3]), abiraterone acetate (STAMPEDE and LATITUDE), enzalutamide (ARCHES, ENZAMET [4, 5]), and apalutamide (TITAN [6]). In addition, current standard therapy for patients with CRPC apart from ADT includes sipuleucel-T, chemotherapy (docetaxel if no prior use, or cabazitaxel if prior docetaxel), abiraterone acetate, enzalutamide, olaparib and rucaparib (for molecularly selected patients with mutations in DNA damage repair genes), and radium-223 (for bone metastases). However, mCRPC remains a lethal diagnosis, and more
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