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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
Format: Article
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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Summary: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.

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