PMID- 38458891
OWN - NLM
STAT- Publisher
LR  - 20240308
IS  - 2588-9311 (Electronic)
IS  - 2588-9311 (Linking)
DP  - 2024 Mar 7
TI  - Olaparib Combined with Abiraterone versus Olaparib Monotherapy for Patients with 
      Metastatic Castration-resistant Prostate Cancer Progressing after Abiraterone and 
      Harboring DNA Damage Repair Deficiency: A Multicenter Real-world Study.
LID - S2588-9311(24)00050-6 [pii]
LID - 10.1016/j.euo.2024.02.005 [doi]
AB  - BACKGROUND AND OBJECTIVE: Olaparib + abiraterone has a combined antitumor effect 
      in metastatic castration-resistant prostate cancer (mCRPC), but the efficacy of 
      this combination in patients with DNA damage repair (DDR)-deficient mCRPC 
      progressing after abiraterone is unknown. Our aim was to compare the efficacy of 
      olaparib + abiraterone versus olaparib monotherapy for patients with 
      DDR-deficient mCRPC progressing after abiraterone. METHODS: The study included 86 
      consecutive patients with DDR-deficient mCRPC progressing after abiraterone: 34 
      received olaparib + abiraterone, and 52 received olaparib monotherapy. 
      DDR-deficient status was defined as the presence of a DDR gene with a pathogenic 
      or likely pathogenic variant (DDR-PV), or with a variant of unknown significance 
      (DDR-VUS). We assessed progression-free survival (PFS) and overall survival (OS) 
      using the Kaplan-Meier method. Potential factors influencing PFS and OS were 
      compared between the treatment arms using Cox proportional-hazards models. The 
      prostate-specific antigen (PSA) response, the treatment effect across subgroups, 
      and adverse events (AEs) were also evaluated. KEY FINDINGS AND LIMITATIONS: 
      Median follow-up was 9 mo. In the overall cohort, median PFS and OS were 
      significantly longer in the combination arm than in the monotherapy arm (PFS: 6.0 
      vs 3.0 mo; hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.25-0.67; 
      p < 0.01; OS: 25.0 vs 12.0 mo; HR 0.30, 95% CI 0.14-0.67; p < 0.01). PSA 
      responses were significantly higher following combination therapy versus 
      monotherapy. Combination therapy had significantly better efficacy in the DDR-PV 
      and DDR-VUS subgroups, and was an independent predictor of better PFS and OS. AE 
      rates were acceptable. The retrospective nature, small sample size, and short 
      follow-up are limitations. CONCLUSIONS: Olaparib + abiraterone resulted in better 
      PFS and OS than olaparib alone for patients with DDR-deficient mCRPC progressing 
      after abiraterone. These results need to be confirmed by a large-scale 
      prospective randomized controlled trial. PATIENT SUMMARY: Our study shows that 
      the drug combination of olaparib plus abiraterone improved survival over 
      abiraterone alone for patients who have mutations in genes affecting DNA repair 
      and metastatic prostate cancer resistant to hormone therapy. The results provide 
      evidence of a synergistic effect of the two drugs in these patients.
CI  - Copyright (c) 2024 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Xie, Jun
AU  - Xie J
AD  - Department of Urology, Shanghai Tenth People's Hospital, Shanghai Clinical 
      College, Fifth Clinical Medical College, Anhui Medical University, Shanghai, 
      China.
FAU - Guo, Hanxu
AU  - Guo H
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University School 
      of Medicine, Shanghai, China.
FAU - Dong, Baijun
AU  - Dong B
AD  - Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Urology, First Affiliated Hospital of Wenzhou Medical University, 
      Wenzhou, China.
FAU - Jin, Chengqi
AU  - Jin C
AD  - Department of Urology, School of Medicine, Anhui University of Science and 
      Technology, Huainan, China.
FAU - Xu, Qiufan
AU  - Xu Q
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University School 
      of Medicine, Shanghai, China.
FAU - Ding, Li
AU  - Ding L
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University School 
      of Medicine, Shanghai, China.
FAU - Liu, Wujianhong
AU  - Liu W
AD  - Department of Pathology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Dong, Shengrong
AU  - Dong S
AD  - Department of Pathology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Zhao, Tingting
AU  - Zhao T
AD  - School of Life Sciences and Technology, Tongji University, Shanghai, China; 
      Research Institute, GloriousMed Clinical Laboratory, Shanghai, China.
FAU - Yu, Yang
AU  - Yu Y
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University School 
      of Medicine, Shanghai, China.
FAU - Guo, Changcheng
AU  - Guo C
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University School 
      of Medicine, Shanghai, China.
FAU - Yao, Xudong
AU  - Yao X
AD  - Department of Urology, Shanghai Tenth People's Hospital, Shanghai Clinical 
      College, Fifth Clinical Medical College, Anhui Medical University, Shanghai, 
      China; Department of Urology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University 
      School of Medicine, Shanghai, China; Department of Urology, School of Medicine, 
      Anhui University of Science and Technology, Huainan, China. Electronic address: 
      yaoxudong1967@163.com.
FAU - Peng, Bo
AU  - Peng B
AD  - Department of Urology, Shanghai Tenth People's Hospital, Shanghai Clinical 
      College, Fifth Clinical Medical College, Anhui Medical University, Shanghai, 
      China; Department of Urology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University 
      School of Medicine, Shanghai, China. Electronic address: pengbo6908@163.com.
FAU - Yang, Bin
AU  - Yang B
AD  - Department of Urology, Shanghai Tenth People's Hospital, Tongji University School 
      of Medicine, Shanghai, China; Urologic Cancer Institute, Tongji University School 
      of Medicine, Shanghai, China; Department of Urology, School of Medicine, Anhui 
      University of Science and Technology, Huainan, China. Electronic address: 
      yangbnju@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20240307
PL  - Netherlands
TA  - Eur Urol Oncol
JT  - European urology oncology
JID - 101724904
SB  - IM
OTO - NOTNLM
OT  - Abiraterone
OT  - Androgen receptor signaling pathway
OT  - DNA damage repair
OT  - Homologous recombination repair
OT  - Olaparib
OT  - PARP inhibitor
OT  - Precision medicine
OT  - Prostate cancer
OT  - Synergistic effect
EDAT- 2024/03/09 10:42
MHDA- 2024/03/09 10:42
CRDT- 2024/03/08 21:56
PHST- 2023/10/29 00:00 [received]
PHST- 2024/02/07 00:00 [revised]
PHST- 2024/02/16 00:00 [accepted]
PHST- 2024/03/09 10:42 [medline]
PHST- 2024/03/09 10:42 [pubmed]
PHST- 2024/03/08 21:56 [entrez]
AID - S2588-9311(24)00050-6 [pii]
AID - 10.1016/j.euo.2024.02.005 [doi]
PST - aheadofprint
SO  - Eur Urol Oncol. 2024 Mar 7:S2588-9311(24)00050-6. doi: 10.1016/j.euo.2024.02.005.