Evaluating the combination of atezolizumab with neoadjuvant chemotherapy for the treatment of triple-negative breast cancer

Dr Luca Gianni - San Raffaele Hospital, Milan, Italy

The NeoTRIP study is a study that wants to test the potential benefit derived from the addition of an immuno-oncology, particularly in this case atezolizumab, to chemotherapy in women with triple negative early high risk or locally advanced breast cancer. This is done in the neoadjuvant setting for several reasons but after surgery patients also receive an anthracycline containing regimen as adjuvant for four cycles.

What were the results that you found?

We found that the rate of pathological complete response which is a measure of the efficacy of your regimen was similar with or without atezolizumab in these two subgroups of women. This with a chemotherapy consisting of carboplatin and nab-paclitaxel given for eight cycles before undergoing surgery.

Were there any adverse events?

Adverse events were more or less the same with or without atezolizumab with the exception of a higher rate of abnormalities of the liver transaminases associated with the administration of atezolizumab. This was short-lived and without sequelae and long-term effects and usually did not affect the probability of administering cycles later on.

How should a clinician decide whether pembrolizumab or atezolizumab is appropriate?

At this point in time if they were aware of the availability of the drugs it would be an easy call because pembrolizumab administration is associated with an improvement of pathological complete response in this study, KEYNOTE-522, while atezolizumab does not improve the rate of pathological complete response. But the two studies are very different and the endpoint of the NeoTRIP is, indeed, event free survival not pathological complete response. It is selected as event free survival for a reason. When we designed the trial, and also as of today, we have no idea of the value of pathological complete response in the case of immune modulation by this new series of drugs. Because the intervention of these drugs on the immune system may well be something that shows up on long-term without affecting the immediate response. So it is trying to compare two different trials with different goals and with different chemotherapy backbones as they were designed.

What is the potential clinical impact of these results?

For NeoTRIP it is still very, very early and so the clinical impact will have to wait until we have mature data on the effects on event free survival. It will not take much longer because in our trial we selected a patient population that was represented by 50% of locally advanced breast cancer and the other patients were all with very high risk type of disease. Unfortunately we know that usually these patients have an event free survival that drops rapidly after surgery so we will see the results, I expect, in terms of a few years.

Are there any molecular studies being planned?

Yes, we have already fully characterised the PD-L1 expression because it was an element of stratification in our trial. We are rushing in to test for the extent and type of lymphocytic tumour infiltration and we have performed several collections of the tumour and the blood before, after one month and at the end of chemotherapy before surgery. We are performing a series of molecular analyses and immunohistological analyses to see if we can find a predictor associated with better or worse probability of response at this stage or of event free survival at a later stage.