Olaparib and durvalumab in metastatic BRCA wild type triple-negative breast cancer

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Published: 6 Jun 2019
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Dr Zahi Mitri - OHSU Hospital, Portland, USA

Dr Zahi Mitri talks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about results from a trial looking at olaparib and durvalumab in metastatic BRCA wild type triple-negative breast cancer.

He explains that olaparib is approved for treatment for patients with BRCA germline breast cancer and the goal of this study is to see if this combination works for patients outside of that group.

Dr Mitri explains that the study is ongoing and hopes that results will start coming in at the end of the year.

This programme has been supported by an unrestricted educational grant from Pfizer.

We’re presenting on a phase II study that we’re doing of the PARP inhibitor olaparib in combination with an immunotherapy drug, a PD-L1 antibody durvalumab, in metastatic patients with triple negative breast cancer. The goal of this study is to look actually at the potential efficacy of this combination in patients who do not have a BRCA germline mutation. We know that olaparib has been approved in BRCA germline breast cancer that is metastatic and the goal here is to see if this combination actually works outside of that patient population.

We’re doing a series of correlatives as well with this study. So patients come into the trial, get a pre-treatment biopsy and start on olaparib for four weeks. At that time we repeat the biopsy and only at that point do we add the immunotherapy to the PARP inhibitor. So the two biopsies actually allow us to look at the pre-treatment, before any treatment, any therapy effect, and how the olaparib actually impacts the tumour and who is going to be actually benefitting from the addition of the immunotherapy on the back end.

The study is ongoing so we don’t have results yet. We started in January, we have around eight patients on right now. What has been good is that all the patients have been able to go through the study procedures, get the pre on treatment biopsy and some of the patients are already on the trial. We’re hoping to finish the first stage of the study by the end of this year and start having some results to report.

We’re hoping to see that the combination, hopefully, will have some effect in a subset of patients with metastatic breast cancer. There’s really no curative therapy right now for this population and immunotherapy just got approved in combination with chemo but that can still be toxic. Our goal is to see if this combination which has been shown to work in BRCA positive patients, we have seen it in the lab outside of BRCA, if we can see some efficacy then we’re hoping that this will become a regimen that we can use for these patients.

Is there a role for predictive biomarkers?

Yes, what we’re hoping is after the four weeks this on treatment biopsy will be able to show us who potentially will benefit from the addition of the immunotherapy. But what also will be nice is that we’re using this study hopefully as a benchmark to build other arms to the study. The four week biopsy will inform us how the olaparib is affecting the tumour, potential mechanisms of resistance and which drug we need to add on the back end. So we’re using this to test the efficacy of this combination but also hopefully to build the next line of clinical trials based on the information and the biomarkers we develop.

We’re very excited about this study, we’re excited about the scientific platform, that is what we call the SMART platform for our precision oncology group. I’m hoping that we get really good results that benefit our patients.