Abstract:
CONTEXT:There 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. OBJECTIVE:To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. EVIDENCE ACQUISITION: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. EVIDENCE SYNTHESIS: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. CONCLUSIONS: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. PATIENT SUMMARY: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.
journal_name
Eur Uroljournal_title
European urologyauthors
Sathianathen NJ,Koschel S,Thangasamy IA,Teh J,Alghazo O,Butcher G,Howard H,Kapoor J,Lawrentschuk N,Siva S,Azad A,Tran B,Bolton D,Murphy DGdoi
10.1016/j.eururo.2019.09.004subject
Has Abstractpub_date
2020-03-01 00:00:00pages
365-372issue
3eissn
0302-2838issn
1873-7560pii
S0302-2838(19)30693-1journal_volume
77pub_type
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