The Gepar Nuevo is a phase II double-blind randomised study which investigated the addition of durvalumab, which is a checkpoint inhibitor, a PD-L1 inhibitor, to a taxane anthracycline containing regimen in triple negative breast cancer.
So we enrolled 174 patients and they were randomised to receive either durvalumab or placebo, first for two weeks and then chemotherapy was added; it was started with nab-paclitaxel for 12 weeks with 125mg and then followed by EC dose dense for another four cycles.
The window of opportunity phase was closed after 117 patients and then all patients started straight with chemotherapy plus or minus durvalumab or placebo.
The primary endpoint of the study was the pathological complete response rate compared between the two arms and PCR was defined as no invasive and no known invasive residuals in breast and nodes which is the stricter definition we have.
We observed a PCR increase from 44.2% to 53.4% in favour of durvalumab. It was not in the strict sense statistically significant because we only had 174 patients enrolled but the odds ratio of 1.53 was in favour of durvalumab and was also statistically significant.
We observed a couple of interesting observations in the predefined subgroup analyses.
The first one was the greater, much greater, benefit in the window of opportunity part. So it seems that patients who were primed with durvalumab first derived a very large benefit - here the increase was from 51% to 61% PCR rate.
The second group which benefited was the stage 2a and higher which also had a PCR rate with durvalumab of around 60%.
Then the patients who were 40 years or younger who also reached a PCR rate with durvalumab of 69%.
So these were the three main groups. Most interesting was the patients with the window of opportunity.
Overall the safety profile of the addition of durvalumab was very good.
We observed only immune related events related to endocrine disorders of the thyroid glands.
So it was either a hyperthyroidism or a hypothyroidism and otherwise no immune related events which caused any severe reactions were observed.
And those were the events of special interest in the abstract?
Those were the events of special interest, yes.
No other differences between the placebo and the durvalumab arm were observed and, of course, the chemotherapy led to the expected events we had.
Plans for the evaluation or expansion – where to take this trial next?
Yes, that’s a very good question.
We want to continue with the evaluation of durvalumab in triple negative breast cancer and plan a phase III study which will then give the ultimate answer what is the value of a checkpoint inhibitor in early triple negative breast cancer.
But that would have not only the PCR as a primary endpoint but also the disease free or event free survival which is very important when we talk about immunotherapy in breast cancer patients.