An overview of hormonal directed pharmacotherapy for the treatment of prostate cancer

ABSTRACTIntroduction Prostate cancer is the most common malignancy in the male. Androgen-deprivation therapy (ADT) has been the mainstay in the treatment of metastatic prostate cancer however, due to the outgrowth of castration-resistant cell population the disease inevitably progresses to an aggressive, difficult to handle stage.Areas covered We have reviewed the literature regarding hormonal-directed therapy prostate cancer. New agents, namely abiraterone acetate, combined with prednisone, and next generation antiandrogens (enzalutamide, apalutamide and darolutamide) have shown considerable efficacy, not only in patients with metastatic but also in those with non-metastatic disease, either castration resistant (CRPC) or hormone sensitive (HSPC).Expert opinion The addition of abiraterone and of the second-generation antiandrogens to our therapeutic armamentarium has improved prognosis ofprostate cancer in the last decade. Abiraterone is a viable option in patients with metastatic disease (hormone-sensitive and castration-resistant), whereas all next-generation antiandrogens have demonstrated efficacy in terms of metastasis-free and overall survival in non-metastatic CRPC. In addition, enzalutamide has also been found efficacious in mCRPC and mHSPC, while apalutamide in mHSPC. Currently there are no reliable data to indicate a potential superiority of one of these agents over the others in CRPC or HSPC as there are no relevant head to head studies . Sequencing hormone treatment modalities, chemotherapies and immunotherapies have not reached a consensus as yet. Randomized controlled trials are warranted to clearly define the role of novel antiandrogens in the treatment of prostate cancer. The choice of treatment should be individualized following discussion with the patient .KEYWORDS: Prostate cancerandrogen deprivation therapyabirateroneantiandrogensenzalutamideapalutamidedarolutamide Article highlights Abiraterone combined with prednisone has been found to significantly prolong overall survival in patients with mCRPC and mHSPC and is therefore a viable treatment option in these settings.All 3 next generation antiandrogens have been approved in nmCRPC, as they have been demonstrated to improve time to PSA progression as well as metastasis-free and overall survival.In mCRPC, apart from abiraterone, enzalutamide has also been shown to provide a survival benefit and has therefore been approved for treatment.In patients with mHSPC, both enzalutamide and apalutamide has shown efficacy, whereas darolutamide is still being evaluated in this setting.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresA reviewer on this manuscript has disclosed that in the past 36 months, they have been on the Advisory Board for BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals, Lucence Health, IMV, Vial, Syapse, Tempus. They have been a Consultant and on the Scientific Advisory Board (SAB) for Suba Therapeutics, Syapse, Servier, Merck. They have also received research support to their institution from Sanofi (iaward), AstraZeneca, Gilead, Helsinn, Lucence, BMS, EMD Serono, Jazz Therapeutics. They have been a Speaker at BIO – INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, OLE Forum (Mexico), Seagen, Gilead, Natera, Exelixis, Janssen. They have received data safety monitoring committee honorarium from Mereo. They have received writing and editor fees from Uptodate, and Onviv. They declare that the declarations do not impact their ability to review.Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.Additional informationFundingThis paper was not funded.