BMC Medicine (May 2024)

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer

  • 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

DOI
https://doi.org/10.1186/s12916-024-03409-9
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 13

Abstract

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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.

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