Olaparib for Chinese metastatic castration-resistant prostate cancer: A real-world study of efficacy and gene predictive analysis

doi:10.1007/s12032-022-01648-5

科研成果详情

题名	Olaparib for Chinese metastatic castration-resistant prostate cancer: A real-world study of efficacy and gene predictive analysis
作者	Dong, Baijun 1; Yang, Bin 2; Chen, Wei 3; Du, Xinxing 1; Fan, Liancheng 1; Yao, Xudong 2; Xue, Wei 1
发表日期	2022-05
发表期刊	MEDICAL ONCOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Olaparib HRR mutations mCRPC VUS BRCA2 PSA PSA-PFS
其他关键词	JOINT-CONSENSUS-RECOMMENDATION ; DNA-REPAIR ; SEQUENCE VARIANTS ; UNCERTAIN SIGNIFICANCE ; MUTATIONS ; ASSOCIATION ; GUIDELINES ; STANDARDS ; GENOMICS ; COLLEGE
摘要	To evaluate the real-world effectiveness and gene predictive analysis of olaparib in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC), a multicenter, retrospective, real-world study was conducted by involving Chinese patients with mCRPC from December 2017 to June 2021. Homologous Recombination repair (HRR)gene mutation (HRRm) status was identified using targeted next-generation sequencing (NGS). The primary end point includes prostate-specific antigen (PSA) response rate (PSA(50)). Secondary end points include PSA progression-free survival (PSA-PFS), exploratory endpoints include PSA(50), and PSA-PFS in HRRm-negative patients with variants of unknown significance (VUS). Survival rates were analyzed using Kaplan-Meier (KM) plot. A total of 39 eligible patients with a median age of 65 (interquartile range [IQR]: 59.5-69.5) years were included in the study. Overall, 40% (12/30) of the patients with mCRPC achieved PSA(50) and the median PSA-PFS was 3.1 months (95% Confidence interval [CI]: 2.4-7). Furthermore, higher PSA(50) rate and longer PSA-PFS were observed in HRRm-positive patients (PSA(50): 50% [7/14]; median PSA-PFS: 5.3 months, 95% CI: 3.73-10). Among the HRRm-positive patients, those harboring the BRCA2 aberrations experienced best clinical efficacy (PSA(50): 55.5% [5/9] and median PSA-PFS [95% CI]: 9.5 months [4.3, NA]). Clinical benefit was also observed in HRRm-negative patients (PSA50: 31.3% [5/16]; median PSA-PFS [95% CI]:2.05 months [1.5,8]), wherein most patients with a PSA(50) response were carrying VUS (PSA(50): 50% [4/8]; median PSA-PFS [95% CI]: 2.75 months [1.27, NA]). In one patients with mutation in the ATR gene, the PSA level decreased by 62%. Olaparib improved PSA response and prolonged PSA-PFS in Chinese mCRPC patients especially in those carrying HRR mutation. Among the HRR genes, patients with BRCA2 mutation showed the best clinical benefit. Besides, some patients carrying VUS on HRR gene and other DNA damage response (DDR) gene mutations also showed response to olaparib treatment, indicating that the clinical benefits observed in HRR-negative group were driven by VUS and other DDR gene mutation. However, this should be further explored in the future, and more molecular functional studies are needed to reclassify VUS for better clinical treatment decision-making and management of mCRPC.
资助项目	National Natural Science Foundation of China [81572536, 81672920, 81772742, 81702840, 81702542, 31570993]; Science and Technology Commission of Shanghai Municipality [14140901700, 16411969800, 19411967400]; Shanghai Shenkang Hospital Development Center [SHDC12015125, 16CR3049A]; Shanghai Municipal Education Commission [15ZZ058]; Shanghai Municipal Commission of Health and Family Planning [201640247]; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20152215]; Shanghai Jiao Tong University [YG2016ZD08, YG2017MS47, YG2017MS52]; Innovation Fund for Translational Research of Shanghai Jiao Tong University School of Medicine [15ZH4002, PYZY 16-008, PYXJS16-015]
出版者	HUMANA PRESS INC
出版地	TOTOWA
ISSN	1357-0560
EISSN	1559-131X
卷号	39 期号:5 页码:96
DOI	10.1007/s12032-022-01648-5
页数	10
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000798611700005
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	35599270
SCOPUSEID	2-s2.0-85130710793
通讯作者地址	[Xue, Wei]Department of Urology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China ; [Yao, Xudong]Department of Urology,Tenth People’s Hospital,Shanghai Tongji University,Shanghai,China
Scopus学科分类	Hematology;Oncology;Cancer Research
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/148036
专题	附属第一医院
通讯作者	Yao, Xudong; Xue, Wei
作者单位	1.Department of Urology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China; 2.Department of Urology,Tenth People’s Hospital,Shanghai Tongji University,Shanghai,China; 3.Department of Urology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
推荐引用方式 GB/T 7714	Dong, Baijun,Yang, Bin,Chen, Wei,et al. Olaparib for Chinese metastatic castration-resistant prostate cancer: A real-world study of efficacy and gene predictive analysis[J]. MEDICAL ONCOLOGY,2022,39(5):96.
APA	Dong, Baijun., Yang, Bin., Chen, Wei., Du, Xinxing., Fan, Liancheng., ... & Xue, Wei. (2022). Olaparib for Chinese metastatic castration-resistant prostate cancer: A real-world study of efficacy and gene predictive analysis. MEDICAL ONCOLOGY, 39(5), 96.
MLA	Dong, Baijun,et al."Olaparib for Chinese metastatic castration-resistant prostate cancer: A real-world study of efficacy and gene predictive analysis".MEDICAL ONCOLOGY 39.5(2022):96.