Dr. Luca Gianni, president of the Fondazione Michelangelo in Milan, discusses the results of the NeoTRIP trial, which looked to see if adding the immunotherapy medicine Tecentriq (chemical name: atezolizumab) to chemotherapy before surgery for triple-negative breast cancer with a high risk of recurrence could improve the time women lived without the cancer coming back.
Running time: 7:17
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Luca Gianni: I am Dr. Luca Gianni. I come from Milan, and I am responsible for the coordination of clinical status, breast clinical status at the Fondazione Michaelangelo, which has been established many years ago and conducts several trials in the field. We presented today the initial results and initial report of the NeoTRIP trial. The NeoTRIP trial is a trial that is testing the potential benefit of adding the monoclonal atezolizumab to chemotherapy in the neoadjuvant treatment of triple-negative breast cancer.
Atezolizumab is a new drug, an immune drug that blocks the PD-L1 and so doing boosts the anti-tumor effect of the immune system.
Jamie DePolo: And patients may recognize atezolizumab also as Tecentriq, because it is approved to treat certain breast cancers, correct?
Luca Gianni: Yes, that is correct, and indeed in 2018 there was a seminal publication on the New England Journal of Medicine showing that administration of atezolizumab together with nab-paclitaxel was associated with increased response and increased progression-free survival and increased overall survival in women with triple-negative breast cancer, metastatic, with high expression of PD-L1.
Jamie DePolo: So tell us a little bit about your study and how it was different and how your results were different.
Luca Gianni: The results we have are part of the initial analysis and report of these studies and show that there is no difference in terms of pathological complete response [pCR] between women who receive the chemotherapy alone and those who receive chemotherapy with the addition of atezolizumab. I would like to stress that this is just a very preliminary analysis of this trial and that indeed the trial has a primary objective, that of defining event-free survival, which is more efficaciously linked to the probability of cure in women with breast cancer. This would need time and follow-up to understand.
Jamie DePolo: And there was other research presented today looking at a different immunotherapy, looking at Keytruda, and also had a different endpoint looking more at pCR as opposed to event-free survival. That study had more positive results. I know it was a different medicine. It was also a different chemotherapy that it was matched with. So if you could talk a little bit about those differences and why we see the differences in the results, because I want to make sure patients understand exactly what’s going on.
Luca Gianni: What is going on is that they are very different trials, not only because the drugs are different but also because the pembrolizumab was used as a companion of a different chemotherapy in which there were also anthracyclines, and the anthracyclines are known as drugs that potentially boost the immune system. So there may have been a cooperation by anthracyclines in the activity that was observed with pembrolizumab. The other key element of difference is that in the study of pembrolizumab, the primary endpoint was the assessment of pathological complete response. Indeed, they observed a statistically significant difference in favor of the addition of immunotherapy.
The two studies, as I said, are different. When we design our NeoTRIP trial with atezolizumab, what we were concerned about was that we didn’t know — and we still do not know — what is the meaning of pathological complete response when you add an immune drug. The reason being that immune drugs, at the end of the day, may change the ultimate results. Not only patients to achieve a pathological complete response, but to see patients who have still residual disease, and they can do so by obtaining, allow me to say, a vaccine-like effect. Because what you really want to do is not only to take away the tumor and say I have a pathological complete response, but you want that you stay in that state and that the disease doesn’t recur.
This is measured only by event-free survival. So we are still at a very preliminary phase of analysis of the NeoTRIP trial, and it will take time, still, to know whether or not atezolizumab has worked.
Jamie DePolo: Let me ask you one more question. It seems like from the research that was presented this morning as well that looking at either circulating tumor cells or what are called TILs [tumor-infiltrating lymphocytes], which are a type of immune cell that infiltrate the cancer cells, seem to be a very important indicator of whether immunotherapy is going to work, because the immunotherapy then actually, if I’m understanding right, activates those immune cells that are in the cancer cells. I’m assuming that with your further analysis, will you look at things like that to help figure out maybe who immunotherapy works the best in?
Luca Gianni: It is exactly so. What we have done during this trial is to ask women to provide as much tissue and blood as possible for correlative science. This is not just to have useless knowledge but exactly to define a potential predictor of response. Every new drug has the potential of improving the net results but is also the potential of adding toxicity. So we must select the appropriate cases and offer them a therapy that works so that it is reasonable for them to stand additional toxicity because they have a better chance of cure.
We are really rushing in to try and derive as much information as possible from the NeoTRIP collection of tumor samples and blood to have an answer to this problem.
Jamie DePolo: Thank you very much. I appreciate your time.