Research Highlights from the 2016 San Antonio Breast Cancer Symposium, with Julie R. Gralow, MD

December 28, 2016
Download MP3 (13.86 MB/15:17)

In today’s podcast, we’ll discuss some of the new research that was presented at the 2016 San Antonio Breast Cancer Symposium, held December sixth through tenth in San Antonio, Texas. 

Transcript: 

[music]

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

In today’s podcast, we’ll discuss some of the new research that was presented at the 2016 San Antonio Breast Cancer Symposium, held December sixth through tenth in San Antonio, Texas. This podcast will be led by Dr. Julie Gralow, director of Breast Medical Oncology at Seattle Cancer Care Alliance. Dr. Gralow is a professor in the Medical Oncology Division of the University of Washington School of Medicine and a member of the Clinical Research Division at Fred Hutchinson Cancer Research Center.

ASCO would like to thank Dr. Gralow for summarizing this research.

Dr. Gralow: Hi. This is Dr. Julie Gralow from the University of Washington in the Seattle Cancer Care Alliance in Seattle, Washington. I'm here to talk about some highlights from the 2016 San Antonio Breast Cancer Symposium. This symposium is held every December in Texas. This is our 39th year, and it's a nice combination of laboratory research, clinical research and everything in between that we call translational research. I picked out a few highlights that I thought that patients might be interested in.

First, I'd like to talk about some studies that related to endocrine therapy. About 75% of breast cancers express the estrogen receptor and drugs that target the estrogen receptor are called endocrine or hormonal therapies. At San Antonio this year, we had some interesting presentations both in early stage breast cancer related to endocrine therapy and in advanced or metastatic breast cancer.

So first, let's talk about the early stage breast cancer trials of estrogen receptor targeted drugs. The background here is that we know that in pre-menopausal women, tamoxifen is the standard of care and we have recent data that suggests that longer duration use of tamoxifen—up to 10 years—or maybe suppressing the ovaries in addition to tamoxifen is better than the old standard of 5 years of tamoxifen. So in the post-menopausal setting where 5 years of a class of drugs called aromatase inhibitors are the standard, we saw some presentations looking at whether longer duration of aromatase inhibitors—more than 5 years—would be better. There are 3 main aromatase inhibitors that we use in clinic in early-stage breast cancer, and they are letrozole, also known as Femara; anastrozole, also called Arimidex; and exemestane, also known as Aromasin.

So we saw 3 studies at San Antonio that were looking at longer duration of aromatase inhibitor use. Two of them were done in Europe and those were the Data study and the Ideal study, both studies of about 2,000 patients where patients had had some prior endocrine therapy and then were randomized to longer duration aromatase inhibitor or shorter duration aromatase inhibitor. Neither of those trials showed a benefit for continuing the aromatase inhibitor longer when we looked at their main endpoint which was recurrences or disease-free survival, being alive without a recurrence.

An even bigger trial which was done in North America was called the NSABP B-42 trial. This was a trial of almost 4,000 patients that took patients who were finishing 5 years of some combination of tamoxifen or an aromatase inhibitor and randomized them to get a placebo versus an additional 5 years of an aromatase inhibitor. And additionally, this big trail also was negative for an improvement in what we call disease-free survival or reducing recurrences. And we didn't see at this early time point, this early look at this trial, a reduction in deaths due to breast cancer either.

So with these 3 trials, we also know that there had been a fourth trial presented earlier this year at ASCO in June that had shown a small but real difference. That trial was called the MA.17 trial. So we spent a lot of time talking about what was the difference between these trials, would we recommend when we go back into clinic after this meeting longer-duration aromatase inhibitors. And I think the important thing is that while 1 out of a total of 4 trials now, the 1 that was presented back in June showed a small reduction in recurrence. Most of the patients in either arm of the study, the groups that got longer or the standard duration of endocrine therapy were doing well, with no recurrence and no death. And these 3 trials really had negative results that did not show benefit for longer duration therapy, and there are more toxicities from continuing these drugs for more years.

So I think the conclusion of this is that, while we do have some proven strategies that show that at least in some patients 10 years of tamoxifen is better than 5 or we can do things that are better than 5 years of tamoxifen. In post-menopausal women right now, I think we really aren't sure if there are any women who really benefit from longer duration aromatase inhibitor. So that's a really important finding.

Still in the theme of estrogen receptor targeted therapies, but now moving into the metastatic setting, we had presentations of different classes of drugs that can be added to estrogen targeted therapy, that can either enhance the effectiveness of endocrine therapy or help overcome resistance to endocrine therapy. We already have a couple of classes of drugs where there is a drug approved that can be added to endocrine therapy in metastatic or advanced breast cancer. We have a drug called everolimus or Afinitor which is what we call an mTOR inhibitor and that was FDA approved in 2012 in metastatic breast cancer. And we have a cell cycle or CDK 4/6 inhibitor called palbociclib or Ibrance that was first FDA approved just in 2015.

So what we saw at San Antonio was a third class of drugs that is being studied to overcome resistance or enhance efficacy of endocrine therapy and that's a class of drugs called PI3-kinase inhibitors, another pathway that interacts with the estrogen receptor pathway. We saw the presentation at San Antonio of a trial called the BELLE-3 trial which was a trial in metastatic breast cancer patients who were postmenopausal and they'd had progression after a few prior therapies. And they were randomized to get another class of endocrine therapy called fulvestrant or Faslodex, and half of them got a PI3-kinase inhibitor called buparlisib and half of them got a placebo. So the BELLE-3 trial showed that there was an improvement in what we call progression-free survival, how long the patient and the tumor goes until the tumor starts to progress again and there was an improvement in tumor response by adding the PI3-kinase inhibitor.

Now, buparlisib and other PI3-kinase inhibitors do have side effects including some liver irritation, and an increase in liver function test, and some depression and anxiety. So it's not an entirely benign drug, but I bring up this study because it is showing some signs of activity and there are several PI3-kinase inhibitors like buparlisib that are in later stage studies meaning they're getting close to being evaluated for possible FDA approval. One important thing that we found in the BELLE-3 trial is that we can actually do a test that predicts for which estrogen receptor positive tumors might benefit from a PI3-kinase inhibitor. We're looking for mutation in the PI3-kinase gene. So, that is something that if these drugs get approved, we'll probably be looking at.

In HER2-positive metastatic breast cancer which it's about 20 to 25% of breast cancers that expressed the HER2 gene and half are estrogen receptor positive and half are estrogen receptor negative, we didn't really have any big blockbusters in my opinion in the HER2 arena. But we did do some looking at those tumors that express both HER2 and estrogen receptor, and looking at combinations of HER2 antibodies and estrogen receptor antibodies.

The PERTAIN trial was a trial in the metastatic setting looking at combinations of HER2 antibodies and aromatase inhibitors—those estrogen receptor targeted drugs—and I think what they showed was that you can safely combine these drugs, that patients can have a good response. And in the PERTAIN trial, they looked at whether adding 2 antibodies that target HER2 was better than 1 and it did show that adding 2 antibodies—trastuzumab which is Herceptin and pertuzumab which is Perjeta—was a little bit better than just adding 1 antibody. But it was only a little bit better and these were expensive drugs. So I think we'll need to think about that a little bit more in the future.

In triple negative breast cancer, that's breast cancer that's negative for estrogen receptor, progesterone receptor, and HER2 receptor, we did see some interesting data. And about 15 to 20% of breast cancers are what we call triple negative. And actually, interestingly, we're learning that there are at least 6 subtypes of triple negative breast cancers. So 1 size doesn't fit all here. But the 1 type of therapy I'm going to highlight in triple negative breast cancer is a class of drugs called PARP inhibitors.

Now, PARP is an enzyme that helps repair DNA and it's needed for the survival of cells that have mutations in BRCA. So BRCA1 and 2 gene mutation carriers can have benefit from these drugs. And PARP is also upregulated in some triple negative breast cancers, so we're interested in looking at drugs that inhibit PARP in both BRCA mutation carriers as well as some triple negative breast cancers. We have 1 PARP inhibitor approved in metastatic ovarian cancers, that's olaparib. And actually, 1 that got approved even after San Antonio, rucaparib, which just got approved.

The PARP inhibitor that I'm going to tell you about was a PARP inhibitor called veliparib which was in the Brocade study. So this was metastatic breast cancer patients who were BRCA1 or 2 mutation carriers and they either got chemo or they got chemo with this PARP inhibitor veliparib. The conclusion of the study was that there were trends towards improvements in how long the tumor went before it progressed and how long the patients survived, and there was a significant difference in how many of the tumors responded and there weren't a lot of toxicities. I think it wasn't an overwhelmingly positive result, but there was a lot of discussion about the very low dose of this drug veliparib that was chosen in the trial. And we have a lot of other trials looking at both BRCA1 and 2-positive breast cancer and Triple Negative Breast Cancer using this class of drugs called PARP inhibitors.

I'm going to close with an interesting trial that looked at quality of life and supportive care and that's the SWOG 1202 trial that was looking to see if it could help woman who were on aromatase inhibitors, who were having a lot of joint and muscle symptoms. That's 1 of the most common side effects of those drugs. So the SWOG 1202 trial looked at a drug called duloxetine or Cymbalta, a drug that's FDA approved to treat different kinds of pain disorders. And the SWOG trial took post-menopausal women with stage 1 to 3 breast cancer who are on any kind of aromatase inhibitor and had musculoskeletal pain above a certain point that got worse when they started their aromatase inhibitor. It was just a quick 12-week study looking at whether duloxetine helped these women and there was a placebo.

Both the duloxetine and the placebo helped with joint pain, but importantly, those in the duloxetine arm had a statistically significant improvement in average joint pain compared to the placebo group as well as other measures of pain and quality of life. There is a little bit of side effects from this drug, mostly low grade, but some GI side effects like constipation and diarrhea, nausea, and dry mouth can happen. So it's not a totally benign drug. But in my patients who are having lots of problems with joint and muscle symptoms from aromatase inhibitors—and I'm trying to encourage them to stay on the drug for 5 years—I think now I would consider trying duloxetine anyway. Other things that have been shown to help in that setting have been exercise and acupuncture as well.

So, that's my summary of highlights from the 2016 San Antonio Breast Cancer Symposium. I think there's lots of hope for better therapies and also therapies that are less toxic. I think those are both themes. Let's see more responses but less side effects. So thanks for your interest and we're looking forward to future improvements in 2017. Thanks a lot.

ASCO: Thank you, Dr. Gralow. To learn more about breast cancer, visit www.cancer.net/breast.  And for more expert interviews and stories from people living with cancer, visit the Cancer.Net Blog at www.cancer.net/blog.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high-quality cancer care. Thank you for listening to this Cancer.Net Podcast.

[music]