Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

6009 - HOXA9 methylation in circulating tumor DNA as a prognostic biomarker in BRCA-mutated ovarian cancer patients treated with PARP inhibitor

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Targeted Therapy;  Genetic and Genomic Testing, Counseling

Tumour Site

Ovarian Cancer

Presenters

Maria Rusan

Citation

Annals of Oncology (2018) 29 (suppl_8): viii332-viii358. 10.1093/annonc/mdy285

Authors

M. Rusan1, R. Fredslund Andersen2, A. Jakobsen1, K.D. Dahl Steffensen3

Author affiliations

  • 1 Dept. Of Oncology, Vejle Hospital Sygehus Lillebaelt, Vejle Sygehus, 7100 - Vejle/DK
  • 2 Dept. Of Biochemistry, Vejle Hospital, 7100 - Vejle/DK
  • 3 Department Of Clinical Oncology, Vejle Hospital Sygehus Lillebaelt, Vejle Sygehus, 7100 - Vejle/DK
More

Resources

Abstract 6009

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.

Legal entity responsible for the study

Vejle Hospital, Vejle, Denmark.

Funding

Vejle Hospital, Abbvie.

Editorial Acknowledgement

Not applicable.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.