DORA: Using olaparib alone or with durvalumab in platinum responsive advanced triple-negative breast cancer

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Published: 12 Jun 2019
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Dr Tira Tan - National Cancer Centre, Singapore

Dr Tira Tan speaks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about the phase II DORA study.

She explains that the trial uses the PARP inhibitor olaparib alone or in combination with the PD-L1 inhibitor durvalumab to treat patients with platinum responsive advanced triple-negative breast cancer, thereby using a maintenance strategy to reduce the toxicities experienced by patients.

Dr Tan says that they are expecting some correlative work to come out of this study that will inform them on which patient populations may benefit most from this approach. She also provides her insights on the potential of PARP inhibitors in other settings.

DORA is our abstract and it’s a randomised study that is evaluating a maintenance therapy of PARP inhibitor or PARP inhibitor in combination with a PD-L1 inhibitor, durvalumab, in patients with metastatic triple negative breast cancer. This is the first study that is actually looking at a maintenance strategy in triple negative breast cancer. We’re phenotypically selecting our patients based on platinum sensitivity so these are patients who are receiving platinum chemotherapy as first or second line therapy. If they have non-progressive disease on the chemotherapy treatment they are eligible to be randomised to receive either PARP inhibitor, olaparib, or olaparib in combination with durvalumab as maintenance therapy thereafter which allows these women an opportunity to potentially receive less toxic treatment as compared to chemotherapy and therefore reduce the side effects that these patients might have with chemotherapeutic treatment.

We are anticipating some nice correlative work that comes out of this study too which could potentially inform us of the right patient population who may benefit from a maintenance strategy as well as if there is an opportunity to broaden out the application and use of PARP inhibitor or PARP inhibitor in combination with PD-L1 inhibitor in triple negative breast cancer.

This is a multinational study and it’s currently open for accrual in three countries – the USA, Korea as well as in Singapore. We’re still in the early phases of recruitment and we’re anticipating the study to continue accruing patients and for us to get a readout by the next year or so.

Moving on to PARP inhibitors in general, is there any potential for PARP inhibitor use to be expanded in a different setting, like the preoperative setting maybe?

Yes, I think we’re going to hear some nice pre-op data today as well about olaparib. But certainly with this study right now PARP inhibitors are licensed for use in patients with germline BRCA mutations and we’re hoping that from this study we might be able to broaden it out to patients who have a homologous recombination deficiency. We’re using platinum sensitivity to enrich our population or increase the chances or likelihood of us being able to identify more patients apart from those who are germline BRCA mutated.

What are your opinions on routine germline testing? Is this something that is being done routinely in the clinic?

It’s different from country to country, it depends. I believe in North America it is fairly routine and certainly in Singapore it is routine for us to offer the option of germline BRCA testing. This is accessible to our patients but because of several regulatory and insurance discrimination it may not be accepted by all the patients at this present moment. But it is routine for us to offer BRCA testing for all our patients, yes.

As I said, this is an important study. It’s the first time that a maintenance strategy has been evaluated in triple negative breast cancer so we are very much looking forward to the results of this study.