Initial results of inhibitor combination against breast and gynaecologic cancers

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Published: 11 Sep 2017
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Dr Shannon Westin - MD Anderson Cancer Center, Houston, Texas

Dr Westin talks with ecancer at the ESMO 2017 Congress in Madrid about the phase I expansion of olaparib and a novel AKT inhibitor (AZD5363) in recurrent ovarian, endometrial and triple negative breast cancer. 

She notes this as one of the arms in the OCTOPUS trial, and details the dosage and cohort composure of patients recruited so far.

Dr Westin describes the tolerance of this combination as promising, and notes other arms and combinations within the trial evaluating alternative combinations.

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

This trial is funnily called the OCTOPUS study because it has multiple arms but we are only presenting today the arm that includes the PARP inhibitor olaparib with the AKT inhibitor AZD5363, so new it doesn’t have a name quite yet.

This was for triple negative breast cancer?

It included triple negative breast cancer, ovarian cancer as well as endometrial cancer. So it was a women’s cancer trial.

What were some of the doses being explored in this arm?

The good news about this study is that the doses had already been explored in detail. So we started at what we thought was going to be the recommended phase II dose which was 300mg b.i.d. of the olaparib in tablet formation as well as 480mg of the AZD5363 which was given on a three day on, four day off schedule.

And that was for cohorts from all of the diseases?

Right, from cohorts of all the diseases. So we had planned for a potential reduction in dose if it wasn’t tolerable. With our first couple of patients we did struggle with some of the side effects and did reduce the dose but then we were able to control those side effects very well and ultimately ended up going back up to that first dose level.

So this was just small numbers for now?

Exactly. So we treated approximately 38 patients.

You mentioned some of the tolerability there, were there any other safety indicators?

The main side effects that we had to work on were nausea and diarrhoea but those are two side effects that are very easy to control. What happened was early on in the study people weren’t as aggressive with some of the pre-medications and responding to the first couple of episodes of diarrhoea. So once our investigators got better at jumping right into it or even pre-medicating patients before they had those side effects it really was a lot easier to tolerate.

Then the question is what next?

The good part about this trial is we did two different things. We had expansions at that dose level amongst all three tumour types, so amongst breast cancer, endometrial and ovarian. We saw overall a 22% response rate, so across all the cohorts, but really intriguingly in endometrial cancer we had a 50% response rate. Now, granted these numbers are small, of the evaluable patients there were eight evaluable patients, but it’s really unheard of to see any kind of response rate that high in endometrial cancer, it has basically almost nothing approved for treatment. So we’re very excited about moving forward with that combination in endometrial cancer.

In addition, as part of the trial we did biopsies before and after treatment. So now we’re doing the translational studies to look and understand who really responded and also what happened in those tissues in the responders as well as in the non-responders because that will help us determine what future combinations would make sense for these patients.

Are there any other arms for the OCTOPUS trial that we should keep an ear out for results coming soon?

Sure. We are likely going to be presenting the results of the other arms, which is olaparib and a drug called AZD2014, vistusertib, I think I got that right, and we’ll be presenting that likely at ASCO in 2018.