Exploratory Biomarker Analysis in the Phase III L-MOCA Study of Olaparib Maintenance Therapy in Patients with Platinum-sensitive Relapsed Ovarian Cancer

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2024 May 16

PMID 38755585

Authors

Huayi Li

Zikun Peng

Jianqing Zhu

Weidong Zhao

Yi Huang

Ruifang An

Hong Zheng

Pengpeng Qu

Li Wang

Qi Zhou

Danbo Wang

Ge Lou

Jing Wang

Ke Wang

Beihua Kong

Xing Xie

Rutie Yin

John Low

Abdul Malik Rozita

Lim Chun Sen

Yong Chee Meng

Kho Swee Kiong

Jihong Liu

Zhiqing Liang

Weiguo Lv

Yaping Zhu

Weiguo Hu

Wei Sun

Jingya Su

Qiqi Wang

Rongyu Zang

Ding Ma

Qinglei Gao

Affiliations

Soon will be listed here.

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.

Citing Articles

Poly-ADP ribose polymerase (PARP) inhibitor regimens for platinum-sensitive ovarian cancer in randomized, double-blind, phase III controlled trials: protocol for a systematic review and network meta-analysis.

Peng X, Liu J Front Med (Lausanne). 2025; 12:1539880.

PMID: 39917064 PMC: 11798772. DOI: 10.3389/fmed.2025.1539880.

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