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BMC Med ; 22(1): 199, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755585

RESUMO

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.


Assuntos
Antígeno B7-H1 , Biomarcadores Tumorais , Quimioterapia de Manutenção , Neoplasias Ovarianas , Ftalazinas , Piperazinas , Humanos , Feminino , Ftalazinas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Piperazinas/uso terapêutico , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Quimioterapia de Manutenção/métodos , Idoso , Adulto , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Proteína BRCA2/genética , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Recombinação Homóloga
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