PARP inhibitor olaparib as treatment for pancreatic cancer patients with BRCA gene mutations

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Published: 2 Jun 2019
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Dr Hedy Kindler - University of Chicago, Chicago, USA

Dr Hedy Kindler talks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about results from the POLO trial looking at the use of the PARP inhibitor olaparib as treatment for pancreatic cancer patients with BRCA gene mutations.

She explains that this trial is the first phase III trial showing that a targeted treatment in a biomarker selective group of pancreatic cancer patients can improve progression free survival.

Dr Kindler reports that patients who received olaparib had a median progression free survival of 7.4 months compared with 3.8 months for those who received the placebo.

Watch the press conference here.

Watch a comment from Dr Suzanne Cole here.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

The POLO trial is the first phase III trial to demonstrate that a targeted treatment in a biomarker selected population of pancreatic cancer patients can improve progression free survival. This was a global study that looked at patients with germline BRCA mutations and the patients received at least four months of platinum-based chemotherapy with no limit to the duration of therapy. They were randomised to receive either olaparib or placebo and what we saw was that those patients who received olaparib had a median progression free survival of 7.4 months compared with 3.8 months for those who received placebo. This was a 47% decrease in the risk of progression or death, the hazard ratio was 0.53.
What we saw was that from six months onwards more than twice the percentage of patients on olaparib were progression free and what was truly remarkable was that 23.1% of patients had a response to olaparib and the median duration of response to olaparib in these patients who had metastatic pancreatic cancer was more than two years. Truly remarkable in a disease with such a dismal prognosis.

I think the standard of care will soon change so that all patients should be offered the option of germline testing for BRCA mutations because they now have a targeted treatment that can help them.

What was really nice with olaparib was that quality of life was maintained over time. Remember, patients receiving chemotherapy it can be quite toxic – FOLFIRINOX causes nausea, diarrhoea, neuropathy, fatigue – and some maintenance treatments enable patients to maintain quality of life while receiving a pill instead of IV chemotherapy. I do think it affects quality of life in a very good way.

For the future work of this research would it be possible to look for somatic mutations instead of germline?

Sure, this is a first step. We have identified that olaparib offers significant benefit to patients with germline mutations. Ongoing and future studies will be looking at the concept of BRCAness, looking at patients with somatic mutations, to see whether we could extend these results to other patients.

What’s next for this research is to look at this in patients with somatic mutations, to look at this in patients with earlier stages of disease and to be able to offer this to our patients.