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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

Background 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 repor...

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Main Authors: Li, Huayi, Peng, Zikun, Zhu, Jianqing, Zhao, Weidong, Huang, Yi, An, Ruifang, Zheng, Hong, Qu, Pengpeng, Wang, Li, Zhou, Qi, Wang, Danbo, Lou, Ge, Wang, Jing, Wang, Ke, Kong, Beihua, Xie, Xing, Yin, Rutie, Low, John, Rozita, Abdul Malik, Sen, Lim Chun, Meng, Yong Chee, Kiong, Kho Swee, Liu, Jihong, Liang, Zhiqing, Lv, Weiguo, Zhu, Yaping, Hu, Weiguo, Sun, Wei, Su, Jingya, Wang, Qiqi, Zang, Rongyu, Ma, Ding, Gao, Qinglei
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Published: BMC 2024
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R Medicine
Online Access:http://eprints.um.edu.my/45227/
https://doi.org/10.1186/s12916-024-03409-9
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spelling my.um.eprints.452272024-09-30T01:49:55Z http://eprints.um.edu.my/45227/ Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer Li, Huayi Peng, Zikun Zhu, Jianqing Zhao, Weidong Huang, Yi An, Ruifang Zheng, Hong Qu, Pengpeng Wang, Li Zhou, Qi Wang, Danbo Lou, Ge Wang, Jing Wang, Ke Kong, Beihua Xie, Xing Yin, Rutie Low, John Rozita, Abdul Malik Sen, Lim Chun Meng, Yong Chee Kiong, Kho Swee Liu, Jihong Liang, Zhiqing Lv, Weiguo Zhu, Yaping Hu, Weiguo Sun, Wei Su, Jingya Wang, Qiqi Zang, Rongyu Ma, Ding Gao, Qinglei R Medicine Background 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. Methods 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). Results 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)]. Conclusions 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. Trial registration NCT03534453. Registered at May 23, 2018. BMC 2024-05 Article PeerReviewed Li, Huayi and Peng, Zikun and Zhu, Jianqing and Zhao, Weidong and Huang, Yi and An, Ruifang and Zheng, Hong and Qu, Pengpeng and Wang, Li and Zhou, Qi and Wang, Danbo and Lou, Ge and Wang, Jing and Wang, Ke and Kong, Beihua and Xie, Xing and Yin, Rutie and Low, John and Rozita, Abdul Malik and Sen, Lim Chun and Meng, Yong Chee and Kiong, Kho Swee and Liu, Jihong and Liang, Zhiqing and Lv, Weiguo and Zhu, Yaping and Hu, Weiguo and Sun, Wei and Su, Jingya and Wang, Qiqi and Zang, Rongyu and Ma, Ding and 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). p. 199. ISSN 1741-7015, DOI https://doi.org/10.1186/s12916-024-03409-9 <https://doi.org/10.1186/s12916-024-03409-9>. https://doi.org/10.1186/s12916-024-03409-9 10.1186/s12916-024-03409-9
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Li, Huayi
Peng, Zikun
Zhu, Jianqing
Zhao, Weidong
Huang, Yi
An, Ruifang
Zheng, Hong
Qu, Pengpeng
Wang, Li
Zhou, Qi
Wang, Danbo
Lou, Ge
Wang, Jing
Wang, Ke
Kong, Beihua
Xie, Xing
Yin, Rutie
Low, John
Rozita, Abdul Malik
Sen, Lim Chun
Meng, Yong Chee
Kiong, Kho Swee
Liu, Jihong
Liang, Zhiqing
Lv, Weiguo
Zhu, Yaping
Hu, Weiguo
Sun, Wei
Su, Jingya
Wang, Qiqi
Zang, Rongyu
Ma, Ding
Gao, Qinglei
Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
description Background 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. Methods 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). Results 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)]. Conclusions 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. Trial registration NCT03534453. Registered at May 23, 2018.
format Article
author Li, Huayi
Peng, Zikun
Zhu, Jianqing
Zhao, Weidong
Huang, Yi
An, Ruifang
Zheng, Hong
Qu, Pengpeng
Wang, Li
Zhou, Qi
Wang, Danbo
Lou, Ge
Wang, Jing
Wang, Ke
Kong, Beihua
Xie, Xing
Yin, Rutie
Low, John
Rozita, Abdul Malik
Sen, Lim Chun
Meng, Yong Chee
Kiong, Kho Swee
Liu, Jihong
Liang, Zhiqing
Lv, Weiguo
Zhu, Yaping
Hu, Weiguo
Sun, Wei
Su, Jingya
Wang, Qiqi
Zang, Rongyu
Ma, Ding
Gao, Qinglei
author_facet Li, Huayi
Peng, Zikun
Zhu, Jianqing
Zhao, Weidong
Huang, Yi
An, Ruifang
Zheng, Hong
Qu, Pengpeng
Wang, Li
Zhou, Qi
Wang, Danbo
Lou, Ge
Wang, Jing
Wang, Ke
Kong, Beihua
Xie, Xing
Yin, Rutie
Low, John
Rozita, Abdul Malik
Sen, Lim Chun
Meng, Yong Chee
Kiong, Kho Swee
Liu, Jihong
Liang, Zhiqing
Lv, Weiguo
Zhu, Yaping
Hu, Weiguo
Sun, Wei
Su, Jingya
Wang, Qiqi
Zang, Rongyu
Ma, Ding
Gao, Qinglei
author_sort Li, Huayi
title Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
title_short Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
title_full Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
title_fullStr Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
title_full_unstemmed Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
title_sort exploratory biomarker analysis in the phase iii l-moca study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
publisher BMC
publishDate 2024
url http://eprints.um.edu.my/45227/
https://doi.org/10.1186/s12916-024-03409-9
_version_ 1811682105564856320
score 13.235796

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