Early ImmunoRx Results in Triple-Negative Breast Cancer 'Put Us in a Difficult Position'

Kathy D. Miller, MD


January 14, 2020

This transcript has been edited for clarity.

Hi. I'm Dr Kathy Miller, professor and associate director of clinical research at the IU Simon Cancer Center. I would like to talk with you about some of the data presented on immune therapy checkpoints at this year's San Antonio Breast Cancer Symposium.

We heard the early results of the KEYNOTE-522 study, looking at pathologic complete response (pCR) rates by adding pembrolizumab to a standard taxane plus carboplatin followed by anthracycline-based chemotherapy. These fascinating results were first reported at the European Society for Medical Oncology (ESMO) meeting and were then shared with us here. This was a large trial powered for event-free survival. At this meeting, we have only the initial pCR data, with a significant improvement in all of the patient subgroups. The degree of checkpoint biomarkers or the combined positive score really did not identify a group of patients with greater or lesser benefit. There was maybe a little more benefit in those patients with anatomically more extensive disease. Certainly, those patients with stage II, node-negative disease still derived a significant improvement.

Next to that, we have to juxtapose the results of an Italian trial with a very similar design, looking at the addition of atezolizumab. There is a slight difference in that they gave only the taxane portion of the chemotherapy before surgery and anthracyclines were given after surgery. That trial was also powered to look at event-free survival. Those data are still maturing, but we did get a look at the pCR rates. There was no difference. There was no difference in those who were PD-L1 positive or PD-L1 negative—no improvement in pCR rates overall.

We also have to recall the GeparNuevo study, which had a very similar design, looking at durvalumab added to anthracycline taxane-based therapy.This study also reported no differences.

I think this puts us in a difficult position.

We have guidance from the US Food and Drug Administration (FDA) suggesting that improvements in pCR could be a route to accelerated approval. These are different drugs, but they all aim to target the same pathway and the same underlying biology. There are small differences in the patient population and the chemotherapy used, but there were major differences in the results.

I find it challenging to think through whether the results of the pCR rates are really telling us that there's something different about pembrolizumab or whether those results are spurious, and perhaps event-free survival will show no difference.

I think this is a space that has become more complicated rather than more clear with these results. In my view, this is not yet standard of care.

It will be fascinating to see how the community reacts to these data and their differences. It will also be fascinating to watch how the FDA views these differences and what actions they may take.

I think it's going to take time to see the results of the event-free survival and really understand what the role of these immune checkpoint inhibitors may have in our patients with early-stage breast cancer. I welcome your thoughts on this challenging area as well.

Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.

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