Biomarker for PARP inhibitor responsiveness in ovarian cancer patients

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Published: 27 Nov 2014
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Prof Elizabeth Swisher - University of Washington, Washington, USA

Prof Swisher talks to ecancertv at the 26th EORTC-NCI-AACR Symposium about data from a phase II trial, ARIEL2, which aims to identify patients with ovarian cancer likely to respond to rucaparib.

ARIEL2 is a trial in patients with recurrent ovarian cancer using the PARP inhibitor drug rucaparib. The purpose of the trial really is to develop a biomarker for PARP inhibitor responsiveness in patients, particularly those patients who do not have known BRCA1 and BRCA2 mutations.

Is there a biomarker?

There isn’t a biomarker currently; we know that women with BRCA1 and BRCA2 mutations are more likely to respond to the drug when they have breast cancer or ovarian cancer but other women may also benefit from the drug and that’s what we want to determine with a biomarker that will predict those patients who will best respond to the drug.

What did your data show?

It looks very promising. The trial requires a biopsy before the patient goes on treatment. So we’re using that tumour specimen to test it for certain characteristics that indicate the tumour has defective DNA repair that will make it respond to the PARP inhibitor. Patients with a BRCA mutation had the best response rate but patients who had the characteristic biomarker for deficiency in this DNA repair pathway also had a much better response rate than patients who were biomarker negative.

Could this be applied to breast cancer?

No, these are ovarian cancer patients so we’re not looking at breast cancer at this point. But certainly we think that this biomarker could apply to other cancer types.

What’s next?

ARIEL2 is being followed already by a study called ARIEL3 and ARIEL3 will use this biomarker prospectively and it’s a phase III randomised placebo controlled trial in women with recurrent ovarian cancer where they’ve responded already to a platinum drug and had a good response and then they will go on rucaparib as maintenance therapy versus placebo.

Will we hear about those results at the next AACR conference?

Yes, and more mature results of ARIEL2 will be presented in mid-2015 as well.