1. Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.
- Author
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Li H, Peng Z, Zhu J, Zhao W, Huang Y, An R, Zheng H, Qu P, Wang L, Zhou Q, Wang D, Lou G, Wang J, Wang K, Kong B, Xie X, Yin R, Low J, Rozita AM, Sen LC, Meng YC, Kiong KS, Liu J, Liang Z, Lv W, Zhu Y, Hu W, Sun W, Su J, Wang Q, Zang R, Ma D, and Gao Q
- Subjects
- Humans, Female, Middle Aged, Aged, Adult, Prospective Studies, Neoplasm Recurrence, Local drug therapy, BRCA2 Protein genetics, Antineoplastic Agents therapeutic use, BRCA1 Protein genetics, Homologous Recombination, Phthalazines therapeutic use, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Piperazines therapeutic use, B7-H1 Antigen, Biomarkers, Tumor genetics, Maintenance Chemotherapy methods
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
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