%0 Journal Article
%T Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.
%A Li H
%A Peng Z
%A Zhu J
%A Zhao W
%A Huang Y
%A An R
%A Zheng H
%A Qu P
%A Wang L
%A Zhou Q
%A Wang D
%A Lou G
%A Wang J
%A Wang K
%A Kong B
%A Xie X
%A Yin R
%A Low J
%A Rozita AM
%A Sen LC
%A Meng YC
%A Kiong KS
%A Liu J
%A Liang Z
%A Lv W
%A Zhu Y
%A Hu W
%A Sun W
%A Su J
%A Wang Q
%A Zang R
%A Ma D
%A Gao Q
%J BMC Med
%V 22
%N 1
%D 2024 May 16
%M 38755585
%F 11.15
%R 10.1186/s12916-024-03409-9
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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).<BR><B>RESULTS: </B>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)].<BR><B>CONCLUSIONS: </B>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.<BR><B>BACKGROUND: </B>NCT03534453. Registered at May 23, 2018.