Authors: (including presenting author): :
Doris H.K. Chan, Shirley X. Li
Affiliation: :
Department of Pharmacy and Pharmacology, The University of Hong Kong
Keyword 1: :
systematic review and meta-analysis
Keyword 2: :
second-generation antiandrogens
Keyword 3: :
prostate cancer
Keyword 6: :
overall survival
Introduction: :
Prostate cancer is prevalent among males around the globe. It is a severely debilitating disease with its complications like bone metastasis at later stage. Some of the patients with CSPC will experience mCSPC, and eventually progress to CRPC with much poorer disease prognosis, due to resistance in the previous effective medications because of various reasons, ranging from gene mutation to AR overexpression. The research gap is the need for systematic review for the selected drugs in CRPC.
Objectives: :
Prostate cancer has been more prevalent around the globe, while androgen deprivation therapy has been the most widely used treatment option for prolonging survival of the patients. Constrained by limited systematic review and meta-analysis on the patient group of CRPC, this study aimed to investigate the efficacy and safety of apalutamide, darolutamide, and enzalutamide, compared to placebo in CRPC patients, with two major endpoints including mOS and mPFS, and subgroup analysis of darolutamide, enzalutamide, and nmCRPC, mCRPC patients, for facilitating evidencebased healthcare decisions for healthcare professionals and policymakers.
Methodology: :
PubMed, Embase, Web of Science and Cochrane were searched on 20th August 2023, for histrelin, relugolix, abiraterone, and the three SGAs, in systematic review, which were recommended but not widely accessible in HK. Meta-analysis of the three SGAs was performed with screening of 2081 literature, with 6 available studies ultimately. Risk of bias assessment, meta-analysis was performed with RoB2 and R, R studio respectively.
Result & Outcome: :
Our major findings in efficacy included second-generation antiandrogens demonstrated superiority over placebo, which was in line with previous studies, with mOS pooled HR of 0.67, [0.60-0.75, 95% CI], and mPFS of 0.37, [0.29-0.47, 95% CI], matched with our hypothesis. Our study demonstrated new findings including more significant benefits in mOS for the mCRPC subgroup compared to the nmCRPC subgroup. Our findings of safety were consistent with previous studies, including enzalutamide was associated with the highest fatigue percentage, while darolutamide revealed the best tolerability. SGAs were proved to be beneficial to CRPC patients, in terms of mOS and mPFS, compared to placebo, with tolerable, major side effects like fatigue and diarrhea. Future directions include studying the mechanism of drug resistance, especially for second-generation antiandrogens, and the sequence of administration of the latest drugs for prolonging survival of CRPC patients safely.
