Sara Hurvitz, MD, Associate Professor of Medicine, Director of Breast Oncology at UCLA and Jonsson Comprehensive Cancer Center talks about the HER2 Climb study.
Interview conducted by Ivanhoe Broadcast News in April 2018.
Tell me a little bit about your study, the HER2 climb study.
Dr. Hurvitz: The HER2CLIMB study is a clinical trial that is evaluating a new drug called tucatinib. Tucatinib is an oral drug–a pill–that targets a protein on the tumor cell called HER2. This study is evaluating whether adding tucatinib to standard of care therapy with capecitabine (an oral form of chemotherapy also known as Xeloda) and trastuzumab (an IV form of HER2 targeted therapy also known as Herceptin) will improve outcomes for women with metastatic HER2+ breast cancer. This is a phase II clinical trial in which women are randomized in a blinded fashion (so women and their doctors aren’t sure whether they are receiving tucatinib or not). All women will receive trastuzumab, all women will receive capecitabine and half of the women will also receive this new drug called tucatinib.
And how does the Tucatinib work?
Dr. Hurvitz: It’s a small molecule that gets inside the cancer cell where it targets the inside of the HER2 receptor and stops it from functioning. Interestingly, there is evidence tucatinib can cross the blood brain barrier. A significant proportion of women who have HER2 positive metastatic breast cancer will develop brain metastases. So, the hope is that this drug will be able to prevent or control brain metastases.
And there are some women that are in the trial that already have brain metastases, is that right?
Dr. Hurvitz: Yes. This trial is distinctive because it’s allowing women on the study who have active untreated brain metastases or brain metastases that have been treated but are now growing again. Most studies will not allow women with uncontrolled brain metastases to enroll. It’s a very unique opportunity for women who have this high risk type of metastatic breast cancer to receive a drug that is potentially going to be effective in that type of disease.
Have you had any preliminary results yet from the HER2?
Dr. Hurvitz: No, this is a blinded study so we don’t know whether or not patients are receiving tucatinib or placebo. I can tell you we’re seeing some nice responses in patients with and without brain metastases but we don’t know yet if that’s due to tucatinib.
When did the study start, when will it stop, when can we start expecting some results?
Dr. Hurvitz: It has been open for some time, right now it’s still actively enrolling. I think the hope is that within the year enrollment will be completed. And then it usually takes a few years before the first results are reported out.
What we were talking about is HER2 used to be a big complicator for breast cancer but that’s changing thanks to research like this.
Dr. Hurvitz: Yes, in the nineteen eighties when the HER2 alteration was first defined in breast cancer it was shown to be the worst type of breast cancer to have. If you had too much HER2 expression on your cancer cell, it meant you had a poor prognosis. Then drugs that target HER2 including trastuzumab were developed and what we’ve seen now, following women who have received trastuzumab and HER2 targeted therapies for this disease, is that their disease is actually one of the better subtypes of breast cancer to have. It now looks like the outcome associated with HER2 positive breast cancer is as good as that for HER2 negative breast cancer.
That’s kind of amazing, that’s an amazing turnabout.
Dr. Hurvitz: It is a huge turnabout and it really just speaks to the fact that when the HER2 alteration is present, leading to overexpression of the HER2 protein on the breast cancer cells, HER2 is the driving force causing the breast cancer to behave in an aggressive fashion. Fortunately, targeting the HER2 protein with drugs like trastuzumab leads to substantial benefits for women and actually is turning the disease from a very poor prognosis subtype of breast cancer into a subtype of breast cancer that’s highly treatable.
What is your hope for results from this trial, a turnaround of this disease or a cure, stopping the progression?
Dr. Hurvitz: This study is only enrolling women who have metastatic breast cancer. And as we understand metastatic breast cancer today, it’s not curable. Now I say that sort of in quotation marks because some patients with metastatic HER2 positive breast cancer have prolonged durable remissions. They may be cured but we won’t know for a very long time. Our hope with this drug is that we will be able to see tumors shrink or disappear – both inside and outside the brain—in patients whose disease is resistand to standard therapies available. And our hope is that it will extend the time that women have disease control. I guess the “pie in the sky” hope is that tucatinib will extend survival. If the results from this study are positive then the natural progression may be to study this drug in early stage breast cancer (in the curative setting) to see if we could improve upon cure rates.
What haven’t I asked you that you think should be included in this story?
Dr. Hurvitz: How well tolerated the drug is.
Excellent side effects, well tolerated.
Dr. Hurvitz: Tucatinib is unique, there are other small molecule inhibiters of HER2 that are FDA approved, one is called Lapatinib and the other is Neratinib. The problem with these inhibitors is that it also hits the molecule called HER1 or EGFR. EGFR is associated with rash and more significantly diarrhea. And the diarrhea can be quality of life limiting and even dangerous in some situations. What’s unique about Tucatinib is its really selective for HER2 so it’s not hitting this other receptor. The hope is, and early data suggests, that we’re going to see less toxicity in terms of rash and diarrhea. The grand hope is that it will not only improve our ability to control breast cancer that’s metastatic but also will do so without increasing toxicity.
Are there side effects?
Dr. Hurvitz: There are side effects again that can be seen with any of these inhibiters. Some patients will have nausea, some patients will have diarrhea and fatigue. This goes along with any medicine that we use for breast cancer. This study will better define the toxicity profile of this drug in combination with standard of care therapy.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Sara Hurvitz, MD
310-829-5471
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