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.
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.
BMC Med. 2024 May 16;22(1):199. doi: 10.1186/s12916-024-03409-9.
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.
前瞻性 III 期多中心 L-MOCA 试验（NCT03534453）已证明奥拉帕利维持治疗在亚洲（主要是中国人）铂敏感复发性卵巢癌（PSROC）患者中的疗效令人鼓舞且安全性可控。在这项研究中，我们报告了 L-MOCA 试验的预先计划的探索性生物标志物分析，该分析研究了同源重组缺陷（HRD）和程序性细胞死亡配体 1（PD-L1）表达对奥拉帕利疗效的影响。
使用 ACTHRD 检测，一种基于富集的靶向下一代测序检测，来确定 HRD 状态。使用 SP263 免疫组化检测 PD-L1 表达。将免疫细胞上 PD-L1 表达≥1%定义为 PD-L1 阳性。采用 Kaplan-Meier 法分析无进展生存期（PFS）。
这项探索性生物标志物分析包括 225 名患者，检测了 HRD 状态 [N=190；阳性，N=125（65.8%）]、PD-L1 表达 [N=196；阳性，N=56（28.6%）] 和 BRCA1/2 突变状态（N=219）。HRD 阳性患者的中位 PFS 长于 HRD 阴性患者[17.9 个月（95%CI：14.5-22.1）比 9.2 个月（95%CI：7.5-13.8）]。PD-L1 主要在免疫细胞上表达。在种系 BRCA1/2 突变的患者中，免疫细胞上的 PD-L1 阳性表达与中位 PFS 缩短相关[14.5 个月（95%CI：7.4-18.2）比 22.2 个月（95%CI：18.3-NA）]。相反，在野生型 BRCA1/2 的患者中，免疫细胞上的 PD-L1 阳性表达与中位 PFS 延长相关[20.9 个月（95%CI：13.9-NA）比 8.3 个月（95%CI：6.7-13.8）]。
HRD 仍然是亚洲 PSROC 患者奥拉帕利疗效增强的有效生物标志物。在种系 BRCA1/2 突变的患者中，PD-L1 阳性表达与奥拉帕利疗效降低相关，但在野生型 BRCA1/2 的患者中，PD-L1 阳性表达与奥拉帕利疗效改善相关。
NCT03534453。于 2018 年 5 月 23 日注册。
