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dc.contributor.authorSathianathen, Niranjan J-
dc.contributor.authorKoschel, Samantha-
dc.contributor.authorThangasamy, Isaac A-
dc.contributor.authorTeh, Jiasian-
dc.contributor.authorAlghazo, Omar-
dc.contributor.authorButcher, Georgiana-
dc.contributor.authorHoward, Harriet-
dc.contributor.authorKapoor, Jada-
dc.contributor.authorLawrentschuk, Nathan-
dc.contributor.authorSiva, Shankar-
dc.contributor.authorAzad, Arun-
dc.contributor.authorTran, Ben-
dc.contributor.authorBolton, Damien M-
dc.contributor.authorMurphy, Declan G-
dc.identifier.citationEuropean urology 2019; online first: 31 October-
dc.description.abstractThere have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy. To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease. We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons. Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients. Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.-
dc.subjectAndrogen receptor-targeted therapies-
dc.subjectHormone sensitive-
dc.subjectProstate cancer-
dc.titleIndirect Comparisons of Efficacy between Combination Approaches in Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Network Meta-analysis.-
dc.typeJournal Article-
dc.identifier.journaltitleEuropean urology-
dc.identifier.affiliationUniversity of Sheffield Medical School, Sheffield, UKen
dc.identifier.affiliationDivision of Radiation Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australiaen
dc.identifier.affiliationSir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australiaen
dc.identifier.affiliationDepartment of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australiaen
dc.identifier.affiliationDivision of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australiaen
dc.type.austinJournal Article-
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