HOXA9 methylation in circulating tumor DNA as a prognostic biomarker in BRCA-mutated ovarian cancer patients treated with PARP inhibitor

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Abstrakt

Background

Quantification of circulating tumour DNA methylation is a promising novel approach for predicting and monitoring treatment efficacy in cancer. The currently frequently employed biomarker CA-125, has been recently shown to not be prognostic for overall survival in platinum-resistant patients, making it further relevant for identifying novel biomarkers. HOXA9 promoter methylation has been observed in a large proportion of patients with high grade serous ovarian carcinoma (OC), and hypermethylation of HOXA9 is associated with worse progression-free survival and overall survival. The aim of the current study was to investigate whether HOXA9 methylation at baseline and during treatment, could predict treatment efficacy in BRCA-mutated ovarian cancer patients treated with the PARP inhibitor, Veliparib.

Methods

Plasma from OC patients was retrieved at baseline before initiation of daily oral single agent Veliparib, as well as following each treatment cycle, as part of a phase II investigator initiated trial (NCT01472783). DNA was purified from 4 ml of plasma, bisulfite converted and analysed by droplet digital PCR with a HOXA9 methylation-specific assay. Beta-2-microglobulin alleles/mL were used for normalization, and the fractional abundance of methylated HOXA9 was calculated.

Results

32 patients were enrolled in a phase II trial, of which 24 had methylated HOXA9 at baseline. There was no significant different in overall survival based on HOXA9 methylation at baseline (p = 0.4), however patients with HOXA9 methylation following three treatment cycles had a significantly worse overall survival compared to patients with non-methylated HOXA9 (median overall survival was 8 months vs. 19 months for patients with methylated vs. non-methylated HOXA9, respectively, p = 0.0001). A similar trend was noted for progression free survival.

Conclusions

Methylation of HOXA9 detected in circulating tumor DNA may serve as a prognostic and treatment efficacy biomarker in BRCA-mutated ovarian cancer patients undergoing treatment with PARP inhibitors.

Clinical trial identification

NCT01472783.
OriginalsprogEngelsk
Artikelnummer954P
TidsskriftAnnals of Oncology
Vol/bind29
Udgave nummerSuppl. 8
Antal sider1
ISSN0923-7534
DOI
StatusUdgivet - 20. okt. 2018
BegivenhedESMO 2018 Congress: Securing access to optimal cancer care - Munchen, Tyskland
Varighed: 19. okt. 201823. okt. 2018
https://www.esmo.org/Conferences/ESMO-2018-Congress

Konference

KonferenceESMO 2018 Congress
LandTyskland
ByMunchen
Periode19/10/201823/10/2018
Internetadresse

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