Studies to Watch at SABCS 2014

Carlos L. Arteaga, MD

Ahead of our coverage of the San Antonio Breast Cancer Symposium, taking place December 9–13, we discuss key presentations at the meeting with Dr. Carlos Arteaga, director of the breast cancer program and professor of medicine and cancer biology at the Vanderbilt-Ingram Cancer Center in Nashville. 

 -Interviewed by Anna Azvolinsky 

Cancer Network: Let’s start with HER2-positive breast cancer. What are the presentations, if any, that you are looking forward to at the meeting?

Dr. Arteaga: For HER2, there is one presentation that is going to look at the affect of tumor-infiltrating lymphocytes, that is TILs, measured in biopsies of patients that were enrolled in the seminal adjuvant trials of chemotherapy and trastuzumab. And those studies will show whether there is or isn’t a correlation between TILs and response. This study will shed some light into the possibility that the immune cells in the host may be important for the benefit to the action of trastuzumab and the benefit on those patients derived from trastuzumab.

Cancer Network: The results from the phase II trial with the PI3K inhibitor, pictilisib, in women with estrogen receptor (ER)-positive disease is going to be presented. PI3K inhibitors on their own have not yet been successful in breast cancer in terms of efficacy. Can you discuss the rationale for the trial and what do we know so far about which patients may benefit from PIK3 inhibitors in general?

Dr. Arteaga: Well, I think that PI3 kinase inhibitors have shown activity in breast cancer. We know already that, like any targeted therapy, their effect is going to be very limited in use as single agents, so I want to make that comment, because some people have discarded them as active agents. And I think that’s unfortunate. This study, FERGI, will show a comparison between fulvestrant and pictilisib and fulvestrant alone in patients with metastatic ER-positive breast cancer who have progressed on anti-estrogen therapy in the metastatic setting. Also, it comes with a biomarker analysis that will tell us whether PIK3CA mutations are associated or not with benefit. Again, this is a burning question we all have as to whether there is a biomarker, a genomic biomarker that can inform which patients will benefit from these drugs. Again, we don’t know that yet, and this will be one of the first studies to ever look into that in breast cancer in a randomized fashion, as well as more on the safety of this combination. There are some side effects of these drugs that we need to learn how to handle. Particularly, we consider that these drugs may move to the adjuvant setting where patients may be on this treatment for a long, long time.

Cancer Network: Are there other ER-positive disease abstracts that you are also looking forward to at the meeting?

Dr. Arteaga: Yes. There is one that will be an update of the SOFT trial. It’s a very important study that will look at the effect of ovarian suppression plus tamoxifen in women with ER-positive early premenopausal breast cancer. It’s a huge, hugely important study. Again, we know that in ER-positive disease, the majority of patients really don’t benefit from chemotherapy whatsoever. The challenge is how to optimize the anti-estrogen treatment in these women, particularly premenopausal women where we have to worry about the rate of recurrence for a long time because they are going to be alive for a long time, being young at the time of their diagnosis. So these are very important studies and it may very well be that the major highlight of the meeting, the SOFT trial.

Cancer Network: An increasing number of tumor types are being tested for their response to either anti-PD1 and PD-L1 immune checkpoint inhibitor antibodies. And at San Antonio, the first results of these programmed cell death antibodies in breast cancer are going to be presented. Can you talk about your perspective on using immunotherapy as a treatment in breast cancer?

Dr. Arteaga: Well, I think it is still investigational. I am aware of the exciting results in other tumor types. Just this week there are five papers in Nature that look at the effect of these checkpoint inhibitors. Missing in action in those papers is breast cancer! But, there is no reason not to suspect that some of these effects will also be seen, and no reason to deny the possibility that some of these same results will be seen, at least in a cohort of patients with breast cancer. I think the emphasis has been on triple-negative breast cancer, maybe because that is the tumor where we still have a lot of progress to make. I would not rule out that if there are effects of these immunotherapies, they will also happen in ER-positive tumors and HER2-positive, but again, triple-negative seems to be the battleground that has been chosen to get the early data as to whether these inhibitors work or not. There will be a phase I trial presentation of pembrolizumab. Again, that shows a suggestion of activity in patients with triple-negative breast cancer. The challenge is that, again, we just don’t have a biomarker. We just don't know which patients will benefit or not. I would hope that information at the meeting would reassure us that there is a biomarker or that we have to continue to seek one, because otherwise we will continue to be destined to try these therapies in the dark. We have had other situations that have not worked out. What if it is only a limited group of patients that benefit, and we treat a whole population? It may well be that we miss the effect of these drugs and it will give these drugs a bad name, just because we did a trial wrong. So I am looking forward to these presentations, but again I am focused as a laser as to whether the presenters will focus on a biomarker that will tell us who are the patients that will benefit and who are the ones where we should not try these new drugs.

Cancer Network:Thank you so much for joining us today, Dr. Arteaga. Enjoy the meeting!

Dr. Arteaga: My pleasure.