PARP inhibitors are most effective in homologous recombinant (HR) deficient tumors. There are
clear indications that besides BRCA1 or BRCA2 mutated EOC, there is an additional group of
EOC having deficiencies in HR (i.e. BRCAness) that might benefit from treatment with PARP
inhibitors. Assessment of HR in high grade EOC might therefore serve as a better predictive
biomarker and allow the identification of a larger group of patients that could benefit most
from platinum based chemotherapy and maintenance treatment with a PARP inhibitor. We recently
developed a robust ex vivo functional assay (RAD51 assay;) to test HR in viable tumor tissue.
In the proposed study, we will evaluate whether the RAD51 assay predicts sensitivity to
therapy with olaparib, in patients with recurrent EOC. With the RAD51 assay we aim to
identify a larger number of patients who will benefit from treatment with the PARP inhibitor
olaparib than patients with a germline or somatic BRCA mutation only. Furthermore, we aim to
identify molecular markers (including genomic markers) that are associated with the outcome
of the RAD51 assay. Finally, we will explore whether these molecular markers can be measured
in liquid biopsies by analysing ctDNA.
Phase:
Phase 2
Details
Lead Sponsor:
Leiden University Medical Center
Collaborators:
Erasmus Medical Center University Medical Center Groningen