PMID- 36959793
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230325
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Comparison of doublet and triplet therapies for metastatic hormone-sensitive 
      prostate cancer: A systematic review and network meta-analysis.
PG  - 1104242
LID - 10.3389/fonc.2023.1104242 [doi]
LID - 1104242
AB  - BACKGROUND: The best choice of first-line treatment for metastatic 
      hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the 
      effectiveness and safety determined in randomized clinical trials of doublet and 
      triplet treatments for mHSPC. METHODS: Medline, Embase, Cochrane Central and 
      ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible 
      studies were phase III randomized clinical trials evaluating androgen deprivation 
      treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), 
      novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies 
      (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included 
      overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse 
      events (AEs). Subgroup analyses were performed based on tumor burden. The effects 
      of competing treatments were assessed by Bayesian network meta-analysis using R 
      software. RESULTS: Ten trials with 12,298 patients comparing nine treatments were 
      included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 
      0.52 [95% CI 0.39-0.70]), but its advantages were all statistically insignificant 
      compared with other therapy options except for DOC+ADT (OR 0.68 [95% CI 
      0.53-0.88]) and RT+ADT (OR 0.57 [95% CI 0.40-0.80]). In terms of PFS, 
      enzalutamide(ENZA)+DOC+ADT (OR 0.32 [95% CI 0.24-0.44]) and abiraterone and 
      prednisone (AAP) +DOC+ADT (OR 0.33 [95% CI 0.25-0.45]) ranked best. For patients 
      with high volume disease (HVD), low volume disease (LVD), and visceral 
      metastases, the optimal therapies were AAP+DOC+ADT (OR 0.52 [95% CI 0.33-0.83]), 
      apalutamide+ADT (OR 0.52 [95% CI 0.26-1.05]) and DARO+DOC+ADT (OR 0.42 [95% CI 
      0.13-1.34]), respectively. For safety, AAP+DOC+ADT (OR 3.56 [95% CI 1.51-8.43]) 
      ranked worst with the highest risk of grade 3-5 AEs. CONCLUSIONS: Triple 
      therapies may further improve OS and PFS but may be associated with a decrease in 
      safety. Triplet therapies could be suggested for HVD patients, while doublet 
      combinations should still be preferred for LVD patients. SYSTEMATIC REVIEW 
      REGISTRATION: 
      https://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier 
      CRD4202303117.
CI  - Copyright (c) 2023 Wang, Li, Zhao, Li, Tang, Guan, Sun, Gu and Li.
FAU - Wang, Lei
AU  - Wang L
AD  - Wu Jieping Urology Center, Peking University Shougang Hospital, Beijing, China.
FAU - Li, Chunxing
AU  - Li C
AD  - Department of Pharmacy, Aerospace Center Hospital, Beijing, China.
FAU - Zhao, Zichen
AU  - Zhao Z
AD  - Wu Jieping Urology Center, Peking University Shougang Hospital, Beijing, China.
FAU - Li, Xiaojian
AU  - Li X
AD  - Wu Jieping Urology Center, Peking University Shougang Hospital, Beijing, China.
FAU - Tang, Chong
AU  - Tang C
AD  - Department of Orthopedics, Peking University Shougang Hospital, Beijing, China.
FAU - Guan, Zhenpeng
AU  - Guan Z
AD  - Department of Orthopedics, Peking University Shougang Hospital, Beijing, China.
FAU - Sun, Feng
AU  - Sun F
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Peking 
      University Health Science Center, Beijing, China.
FAU - Gu, Jin
AU  - Gu J
AD  - Gastrointestinal Cancer Center, Peking University Cancer Hospital, Key Laboratory 
      of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 
      China.
AD  - Department of Gastrointestinal Surgery, Peking University Shougang Hospital, 
      Beijing, China.
FAU - Li, Ningchen
AU  - Li N
AD  - Wu Jieping Urology Center, Peking University Shougang Hospital, Beijing, China.
LA  - eng
PT  - Systematic Review
DEP - 20230307
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10028133
OTO - NOTNLM
OT  - chemotherapy
OT  - combination therapy
OT  - hormonal therapy
OT  - prostate cancer
OT  - radiation therapy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/03/25 06:00
MHDA- 2023/03/25 06:01
PMCR- 2023/01/01
CRDT- 2023/03/24 02:13
PHST- 2022/11/21 00:00 [received]
PHST- 2023/02/20 00:00 [accepted]
PHST- 2023/03/24 02:13 [entrez]
PHST- 2023/03/25 06:00 [pubmed]
PHST- 2023/03/25 06:01 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1104242 [doi]
PST - epublish
SO  - Front Oncol. 2023 Mar 7;13:1104242. doi: 10.3389/fonc.2023.1104242. eCollection 
      2023.