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Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer

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资源类型：
Pubmed体系：
作者：
Li Huayi[1,2] * ; Peng Zikun[1,2] * ; Zhu Jianqing[3] * ; Zhao Weidong[4] * ; Huang Yi[5] ; An Ruifang[6] ; Zheng Hong[7] ; Qu Pengpeng[8] ; Wang Li[9] ; Zhou Qi[10] ; Wang Danbo[11] ; Lou Ge[12] ; Wang Jing[13] ; Wang Ke[14] ; Kong Beihua[15] ; Xie Xing[16] ; Yin Rutie[17] ; Low John[18] ; Rozita Abdul Malik[19] ; Sen Lim Chun[20] ; Meng Yong Chee[21] ; Kiong Kho Swee[22] ; Liu Jihong[23] ; Liang Zhiqing[24] ; Lv Weiguo[16] ; Zhu Yaping[25] ; Hu Weiguo[26] ; Sun Wei[4] ; Su Jingya[27] ; Wang Qiqi[27] ; Zang Rongyu[28] ; Ma Ding[1,2] ; Gao Qinglei[1,2] ;
单位： [1]Department of Obstetrics and Gynaecology,National Clinical Research Centre for Obstetrics and Gynaecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Hankou,Wuhan 430030,China. [2]Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education),Hubei Key Laboratory of Tumour Invasion and Metastasis,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Hankou,Wuhan 430030,China [3]Department of Gynaecologic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China. [4]Department of Gynaecologic Oncology, Anhui Provincial Cancer Hospital, Hefei, China. [5]Department of Gynaecologic Oncology, Hubei Cancer Hospital, Wuhan, China. [6]Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China. [7]Department of Gynaecology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital, Beijing, China. [8]Department of Gynaecology Oncology, Tianjin Central Hospital of Gynaecology Obstetrics, Tianjin, China. [9]Department of Gynaecologic Oncology, Affiliated Cancer Hospital of Zhengzhou University, (Henan Cancer Hospital), Zhengzhou,China. [10]Department of Gynaecologic Oncology, Chongqing University Cancer Hospital, Chongqing, China. [11]Department of Gynaecologic Oncology, Liaoning Cancer Hospital, Shenyang, China. [12]Department of Gynaecologic Oncology, Harbin Medical University Cancer Hospital, Harbin, China. [13]Department of Gynaecologic Oncology, Hunan Cancer Hospital, Changsha, China. [14]Department of Gynaecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. [15]Department of Obstetrics and Gynaecology, Qilu Hospital of Shandong University, Jinan, China. [16]Department of Gynaecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [17]Department of Obstetrics and Gynaecology, West China Second University Hospital, Chengdu, China. [18]Cancer Centre @ PHKL, Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia. [19]Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [20]Oncology Department, Hospital Sultan Ismail, Johor Bahru, Malaysia. [21]Gynaeoncology, Hospital Ampang, Ampang, Malaysia. [22]Oncology, Hospital Umum Sarawak, Kuching, Sarawak, Malaysia. [23]Department of Gynaecologic Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China. [24]Department of Gynaecologic Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China. [25]Department of Gynaecology, Shanghai General Hospital, Shanghai, China. [26]Fudan University Shanghai Cancer Centre and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. [27]Department of Medical Affairs, AstraZeneca, Shanghai, China. [28]Department of Gynaecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
出处：
DOI： 10.1186/s12916-024-03409-9

关键词： Platinum-sensitive relapsed ovarian cancer Olaparib PD-L1 expression BRCA1/2 PARP inhibitors Homologous recombination deficiency L-MOCA trial Biomarker

摘要：
The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy.HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS).This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)].HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2.NCT03534453. Registered at May 23, 2018.© 2024. The Author(s).

基金：
This work was supported by AstraZeneca, China, who provided funding for study design, data collection, analysis, interpretation, and decision to submit the manuscript, and is part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 1 区 医学：内科
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：内科
第一作者：
第一作者单位： [1]Department of Obstetrics and Gynaecology,National Clinical Research Centre for Obstetrics and Gynaecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Hankou,Wuhan 430030,China. [2]Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education),Hubei Key Laboratory of Tumour Invasion and Metastasis,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Hankou,Wuhan 430030,China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Obstetrics and Gynaecology,National Clinical Research Centre for Obstetrics and Gynaecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Hankou,Wuhan 430030,China. [2]Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education),Hubei Key Laboratory of Tumour Invasion and Metastasis,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Hankou,Wuhan 430030,China
推荐引用方式(GB/T 7714)：
Li Huayi,Peng Zikun,Zhu Jianqing,et al.Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer[J].BMC Medicine.2024,22(1):199.doi:10.1186/s12916-024-03409-9.
APA：
Li Huayi,Peng Zikun,Zhu Jianqing,Zhao Weidong,Huang Yi...&Gao Qinglei.(2024).Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.BMC Medicine,22,(1)
MLA：
Li Huayi,et al."Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer".BMC Medicine 22..1(2024):199

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