From the Director: A Successful Collaboration to Support People Living with Metastatic Breast Cancer

As the year draws to a close, I’m reflecting on all that we have accomplished in 2016. One of the things I’m most proud of is the ongoing success of Metastatic Trial Search. In 2015, we led an effort in partnership with Breastcancer.org, Living Beyond Breast Cancer, Metastatic Breast Cancer Network, Triple Step Toward the Cure, and the Young Survival Coalition, to develop a tool that would make it easier for women with metastatic breast cancer to find trials that they might qualify for.  We’ve gotten feedback from a number of women that this new, easy-to-use too, which can be accessed from each of our websites, has helped them and others they know. In 2017, the search tool will also be easily accessed from seven other websites—Cancer Support Community, Dr. Susan Love Research Foundation, Metastatic Breast Cancer Alliance, SHARE Cancer Support, Susan G. Komen, Theresa’s Research Foundation, and Triple Negative Breast Cancer Foundation–expanding our reach even more.

      
        
        
             

I truly believe this type of collaboration is what we need to continue to improve services for women living with breast cancer. Look for more to come in 2017, when will add more features to Metastatic Trial Search as well as launch a new clinical trial educational resource specifically for metastatic breast cancer patients.

In this season of giving thanks, I want to publicly thank our funders: Lilly Oncology, Medivation, Nektar, Cascadian Therapeutics, and MacroGenics; the Avon-Metastatic Breast Cancer Program, and the Metastatic Breast Cancer Alliance for their contributions to Metastatic Trial Search.

Wishing you all the best during the holiday season,
Elly

Elly Cohen, PhD
Program Director, BreastCancerTrials.org

December 13, 2016 at 11:35 pm Leave a comment

Studying New Ways to Treat Brain Metastases

brainWhen breast cancer spreads beyond the breast and lymph nodes under the arm to other parts of the body, it is considered stage IV, or metastatic. Not all cancers are equally likely to spread to the same organs. Breast cancer typically spreads to the lungs, liver, bone, and brain.

 

Studies suggest between 15 and 30 percent of metastatic breast cancer patients will develop brain metastases. But the risk of developing brain metastases is not the same for everyone. Patients with triple-negative breast cancer and HER2-positive breast cancer are more likely to be diagnosed with brain metastases than those with other types of breast tumors.

 

Systemic treatments–drugs that move throughout the body–that can kill tumor cells in, say, the lung or liver, are not typically able to kill tumor cells in the brain. That’s because before it can get to the cancer cells, the drug must cross the blood-brain barrier. The blood-brain barrier plays an important role in daily life, by keeping substances that could damage the brain out. But its tight borders have typically prohibited most cancer treatments from getting in. Researchers are trying to develop new drugs and identify existing drugs that can cross the blood-brain barrier.

December 13, 2016 at 11:35 pm Leave a comment

Q & A with Dr. Michelle Melisko, MD

meliskoMichelle Melisko, MD, an oncologist at the UCSF Helen Diller Family Comprehensive Cancer Center, treats breast cancer patients and conducts research on new cancer treatments. BreastCancerTrials.org spoke with Dr. Melisko about advances in treating breast cancer brain metastases and when patients with brain metastases should consider clinical trials.

Q: Are you seeing more breast cancer patients with brain metastases? If so, why do you think that is?

A: We are seeing more breast cancer patients with brain metastases. It’s not that the biology of breast cancer is changing. It’s because we have an increasing number of treatment options and patients are living longer after they’ve been diagnosed with metastatic disease. Also, we are doing imaging more frequently and the scanners we are using are more sensitive, so we are able to pick up brain lesions that are much smaller than we could before.

Q: Should women with brain metastases consider a clinical trial as initial treatment?

A: That is something we’d love to see in the future—that we’d have a number of options for patients who are diagnosed with small brain metastases found on a brain MRI, before they start having symptoms like headaches or loss of function. Right now, some of the radiation techniques used—Gamma Knife and CyberKnife—that target the metastases with focal beams of radiation are about 80 to 90 percent effective and well tolerated. Patients are often offered this form of radiation as soon as they are diagnosed with brain metastases that are small in size or number (generally fewer than 10). For patients with many lesions or large lesions, radiation to the whole brain is the only option. Clinical trials would be a great alternative.

One challenge is that clinical trials often have a minimum size of brain metastases that is required, typically at least 1cm. But with patients getting MRIs as often as every two to three months, we typically find new metastases early, when they are small. And since they can often be treated effectively with Gamma Knife or CyberKnife, patients don’t want to wait to see if they qualify for a trial because they could grow during that time.

Q: What if Gamma Knife or CyberKnife radiation isn’t an option?

A: If it’s not an option because the patient has more than 10 brain metastases, if the metastases are large with a lot of swelling, or because they live in an area where they don’t have easy access to those treatments, they will likely be treated with whole brain radiation. Ideally patients could consider a clinical trial that is investigating a new treatment that researchers think may be effective against brain metastases as well as metastases in other parts of the body.

Q: Is it easy to find these types of trials?

A: The primary problem is that even for patients with progressing brain metastases there are a limited number of trials. There are an even smaller number for patients who have untreated brain metastases. Also, patients rarely have the option to consider a trial before treatment because if they have symptoms they are going to be referred to a radiation oncologist who will likely recommend some form of radiation.

We’d love to have more ways to try new treatments on patients with small brain metastases, using them as a testing ground for new therapies that we think can cross the blood-brain barrier. That is what the LANDSCAPE trial did. It tested a combination of capecitabine (Xeloda) and lapatinib (Tykerb) in HER2-positive metastatic breast cancer patients with previously untreated brain metastases. The treatment was given before the patients had radiation, and the trial showed it was remarkably effective in shrinking the tumors, delaying the need for radiation for six to eight months.

Q: Why do so many trials exclude patients with brain metastases?

A: This is changing. The majority of trials now will allow patients to participate if the brain metastases have been treated and stable for some period of time after treatment. In the past, patients with brain metastases were thought to have such a poor prognosis that researchers didn’t want to have them in a study because that would make it more difficult to determine whether the drug was effective. If a drug is not active in brain metastases, and a patient has brain metastases, then it was seen as stacking the odds against the novel agent in the trial.

Q: What types of new agents appear most likely to be able to cross the blood-brain barrier?

A: That’s really the million-dollar question right now. Historically, we thought it was solely the size of the molecule that determined if it could get through the blood-brain barrier. But now it’s thought that when there are metastases there may actually be a disruption of the blood-brain barrier. And radiation may disrupt the blood-brain barrier even more. This means it is possible more molecules can get in than we originally thought could. But the question is: At what concentration do these treatments need to get in to be effective, and is there something unique about the cells in the brain that make them more resistant to standard treatment?

Q: How can this be studied?

A: One future direction and what UCSF is doing is seeing if there are imaging techniques that might allow us to see if an agent is getting into the brain. There is a phase I trial at UCSF using an agent MM398 [liposomal irinotecan (Onivyde), a drug approved in 2015 to treat metastatic pancreatic cancer]. The original version of irinotecan (Camptosar) appeared to have some activity in the brain and this novel formation of the drug may get into the brain better. (Editor’s note: This compound is being studied in other trials. See list at the bottom of this article or click here to see trials on BreastCancerTrials.org.)

What is novel about the UCSF study is that MM398 is a nanoparticle version of irinotecan and you can take the coating of the particle and load it with a marker that can be imaged. This means the researcher can see if the drug is getting into the brain. I think this will be the future of drug development for brain metastases—to see if the drug is getting into the brain.

Q: Who can enter this trial?

A: This trial is for breast cancer patients with progressing brain metastases who have already had brain radiation and have cancer that recurs or grows in the brain after those treatments.

Q: Is there anything else that makes brain metastases differ from other types of metastases?

A: Again, there are some hints that metastases that travel to the brain might have certain characteristics. For example, certain tumor types like triple negative and HER2-positive are more likely to spread to the brain. So there is a certain biology of tumor that is more likely to get inside the brain, and once these cancer cells get into the brain there may be other markers that become more prevalent and other genes that might be important. But that’s not known. It’s what is being studied right now.

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Clinical Trials for Brain Metastases
You can use Metastatic Trial Search to easily find a list of clinical trials looking at new ways to treat breast cancer brain metastases.

Some of these trials include:
Halaven for Breast Cancer That Has Spread to the Brain
This phase II trial is investigating the effect eribulin mesylate (Halaven®), which is FDA approved to treat metastatic breast cancer, has on brain metastases.

Capecitabine and BKM120 for Triple Negative Brain Metastases
BKM120 is a new, targeted drug that blocks PI3K, a group of proteins that help cancer cells grow. Capecitabine (Xeloda®) is a chemotherapy drug used to treat triple negative breast cancer. Early studies have suggested this drug combination may be able to cross the blood-brain barrier.

Etirinotecan Pegol For Brain Metastases From Breast (or Lung) Cancer
Pegylated irinotecan NKTR-102 is a new version of the chemotherapy drug irinotecan (Camptosar). This phase II study is investigating how well pegylated irinotecan NKTR-102 works in patients with breast (or lung) cancer that has spread to the brain and has not responded to other treatment.

ONT-380 with Xeloda and Herceptin to Treat Advanced HER2+ Breast Cancer
ONT-380 is a new HER2-targeted drug. It is a small molecule that early studies suggest may be able to pass through the blood-brain barrier. In this phase II trial, ONT-380 is given with trastuzumab (Herceptin®) and capecitabine (Xeloda®). (This trial is known as HER2CLIMB.)

Perjeta and Herceptin for HER2-Positive Brain Metastases
Pertuzumab (Perjeta®) and trastuzumab (Herceptin®) are targeted drugs used to treat HER2-positive breast cancer. This study is investigating the safety and effectiveness of giving Perjeta along with a high dose of Herceptin to treat HER2-positive brain metastases. To be eligible, participants must have had their brain metastases recur or progress after radiation therapy.

Abemaciclib for Hormone Receptor-Positive Brain Metastasis
Abemaciclib (LY2835219) is a new type of targeted therapy called a CDK 4/6 inhibitor. Early studies suggest it may be an effective treatment for hormone-sensitive metastatic breast cancer. This study will determine the safety and effectiveness of using abemaciclib to treat patients with hormone-sensitive breast cancer that has spread to the brain.

December 13, 2016 at 11:35 pm Leave a comment

Talking About Metastatic Breast Cancer Trials 

Welcome to our summer newsletter“Talking about Trials” or, more specifically, talking about metastatic breast cancer trials.
No one knows precisely how many people are living with metastatic breast cancer. The Metastatic Breast Cancer Network reports the number is estimated to be more than 155,000. What we do know is that up to 10 percent of women diagnosed with breast cancer have metastatic disease, and that up to 30 percent of all breast cancer cases will become metastatic. We also know that metastatic breast cancer kills about 40,000 women each year.
Clinical trials are important options all breast cancer patients should consider. They are especially critical for those with metastatic disease, because it can give these women access to the new targeted therapies and immunotherapies that are being developed. As this interactive chart developed by Metastatic Breast Cancer Alliance (MBCA) shows, as of July 2015, there were 204 metastatic breast cancer trials underway–and more have been added since then.
To get results, these trials need to enroll close to 27,900 patients. We are proud to be a member of the MBCA research task force, and be contributing to the Alliance’s aim to ensure all women with metastatic breast cancer know their participation in research trials is needed.
As part of this effort, and with support from the Avon-Pfizer Metastatic Grant Program, we worked over the past year with five other breast cancer advocacy groups to launch Metastatic Trial Search, the first and only clinical trial search engine specifically for people with metastatic breast cancer.
In this issue, we speak with two breast cancer researchers who want to see new areas explored in metastatic clinical trials–Dr. Patricia Steeg and Dr. Gabriel Hortobagyi. We hope you enjoy learning about their ideas and insights. We also hope that this issue leaves you inspired to explore trials for yourself as well as share this information with others you know, especially those living with metastatic disease.

Elly Cohen, Ph.D., Program Director, BreastCancerTrials.org

July 6, 2016 at 11:42 pm Leave a comment

Q & A with Dr. Patricia Steeg, Ph.D.

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Dr. Patricia Steeg

To reduce deaths from metastatic breast cancer, Dr. Steeg believes researchers need to conduct a new type of trial—one that would test drugs that laboratory studies have shown can prevent new metastases from developing. BCT spoke with Dr. Steeg about this new approach to clinical trials.

Q: Why do you think changing the way clinical trials are designed can reduce breast cancer deaths?

A: If we change the way trials are designed, we can enroll patients at different points, treat them with different types of targeted therapies, and use different end points that will still be relevant to patients’ quality and quantity of life.

I am advocating for metastasis prevention studies. The bulk of the preclinical data (studies done in cells and mice) says we can prevent metastases much better than we can shrink ones that have formed. So the question is: Is that true or is that just something we see in mice?

Q: How can you find out?

 A: That’s where the problem is. You can’t do an adjuvant trial that enrolls 1,000 people for each drug that might prevent metastases. (Adjuvant treatment is given after surgery to prevent recurrence.) So, I’m advocating we run smaller trials that enroll either super high-risk patients in the adjuvant setting or patients with limited metastases. The endpoint would be the development of a first or a new metastasis.

Q: Why do you think researchers are resistant to trying this?

A: It is something new. Every time I present this concept to oncology groups they say ‘Pat, of course you are right—but this is not the way we have done trials.

There is limited funding for clinical trials and they are going with what they know. So there is an element of habit, of risk-aversion. Also, I don’t think companies are going to fund these kinds of trials because they have yet to lead to a drug that has been approved by the Food & Drug Administration (FDA). It will take a few brave people with money to run these trials and say, ‘Yes, it works.’ Then more will jump in.

You can learn more about all of the breast cancer trials taking place at the NCI Center for Cancer Research here.

Q: How does what you are talking about differ from regular trials?

A: The trials with the high-risk patients would be mini-adjuvant trials to see if they reduce the risk of recurrence. For the patients with metastases, the trial would look at whether the drug prevents more metastases.

Q: Are there drugs that might stop new metastases from developing?

A: They are called Src inhibitors. They target an enzyme in the cancer cell that plays a role in cell movement and colonization—two things that happen in the metastatic process but don’t happen in a cell sitting still. There were two Src inhibitors that were studied in metastatic trials but those trials didn’t show the drug was effective. But what was measured was whether they shrunk existing tumors. Yet, the literature shows that they prevent new tumors—not shrink ones that are already there. And that’s what needs to be measured—whether they prevented new tumors from developing.

Q: If they could prevent new metastases, how might they be used?

A: The Src inhibitor could be given after standard treatment. I think it would be a maintenance regimen. A patient would have the standard of care and then take the inhibitor for a long time. We are seeing this in lung cancer, where studies are having patients take a low dose of a maintenance drug, and seeing some benefit.

Q: Are you going to do this type of trial?

A: At the NCI we are developing a trial to see if the oral chemotherapy drug temozolomide (which is used to treat some types of brain cancer) can prevent new brain metastases. We found in mice that a low dose of the drug will prevent brain metastases. So we are going to enroll patients with 1-5 brain metastases and treat them with stereotactic radiosurgery (radiation directed at the brain metastases) and then randomly assign half to also start on temozolomide. So, it’s following the standard of care and looking to see if we can prevent new metastases.

The trial Dr. Steeg is developing will take place at the NIH Clinical Center in Bethesda, Maryland. You can learn more about all of the breast cancer trials taking place at the NCI Center for Cancer Research here. Some of these trials cover participants travel expenses to and from the NCI.

You can read more about Dr. Steeg’s ideas about clinical trials in this article published in Nature in May 2012. You can listen to her discuss these ideas here

July 6, 2016 at 11:42 pm Leave a comment

Q & A with Dr. Gabriel Hortobagyi, MD

Gabriel-Hortobagyi

Dr. Gabriel Hortobagyi

In 2001, Dr. Gabriel Hortobagyi published an editorial in the Journal of Clinical Oncology that reviewed what was known at that time about treating breast cancer patients with very few metastatic sites. This limited metastases is called oligometastases. BCT spoke with Dr. Hortobagyi about what types of clinical trials are needed to move forward in this research area.

Q: How has research into oligometastases advanced over the past 15 years?

A: This is an uncommon situation, and the problem with uncommon situations is it takes a long time to do research. There’s been very little additional data since I wrote that piece. The reality remains that there is a small percentage of patients with metastases—somewhere around 5 percent—who have oligometastases and, of these, one in three or one in four could potentially be cured with systemic treatment plus surgery or radiation or both.

The data we have show that these patients tend to be younger, in good physical condition and have metastatic disease that can be removed surgically with clean margins in the lungs, liver, brain and maybe some soft tissue. It also seems that patents with hormone-negative tumors are more likely to be cured, which is probably because their tumors are more responsive to chemotherapy.

Q: Does this mean women should have more screening so that more women would be found with fewer metastases?

A: That’s the controversy. It is a huge question, whether we move away from having the guidelines that say no tests should be done regularly and women should just be alert to possible symptoms. Some of us believe that the studies on which those guidelines are based, which were done in the 1980s, need to be repeated with modern technology.

Q: Could this be done?

A: The problem is that it would take 10,000 to 15,000 patients followed for at least five years, and most likely 10 years. And it would cost between $40 and $100 million to demonstrate, or not, that closer monitoring and earlier diagnosis of metastases will identify a subset of patients who could be treated and never develop additional metastases.

Q: Is money the only obstacle?

A: No. There are other concerns. Because so few women develop oligometastases, the majority of the women in the trial would not experience any benefit. So, it is a complicated issue because whenever you deal with uncommon or rare events you face this situation.

Q: Do new technologies create new possibilities?

A: Right now, the tools we have aren’t at a point where we could do this kind of study. But let’s say in two to three years we have the perfect circulating DNA test and we can show that out of 100 patients we find 30 who have circulating DNA and no other abnormality and that all 30 develop metastatic disease—and none of the others do. Then we’d have something much more solid and something we can rely on. But we don’t have that today.

Also, having a test like that means we wouldn’t need such a large clinical trial. We’d only need to identify 200 patients who test positive on the circulating DNA test and then randomize them to treatment or no treatment and that would only cost maybe $3 million as opposed to 40 or 100 million.

Q: Are we getting closer to that type of test?

A: We’re doing research right now to develop this kind of circulating DNA test, with clinical trials at MD Anderson and through SWOG. (SWOG is a worldwide network of researchers that is part of the NCI’s National Clinical Trials Network.)

I know it’s frustrating for patients. It seems like, ‘why are these guys taking all their sweet time doing this when women are dying of breast cancer’ and I am acutely aware of this frustration. But, unfortunately, this is the way things work and it’s the reality of clinical trials. We need to develop solid preliminary data before we can move to more advanced trials. Most of the trials we complete are negative and they don’t move the field forward they just tell us things don’t work. But we still have to do them.

You can learn about trials open at MD Anderson here.

You can learn more about SWOG-sponsored trials here.

July 6, 2016 at 11:41 pm Leave a comment

Cancer Registry Studies: At Least One for Everyone

clipboard2When thinking about breast cancer research, clinical trials investigating new drug treatments are often the first thing that comes to mind. But there is another type of research study that tends to get much less attention: breast cancer registry studies.

Most people are familiar with the concept of a registry, either having created one for a wedding or new baby or selected a gift from one for a bride or groom. These types of registries are well-organized lists of the gifts a person is hoping to receive. A registry study is similar: It is a well-organized set of questions. But instead of giving a gift, you give answers to the researchers’ questions. In some cases, you also provide a blood or tumor sample that researchers can use in the future. This can help them identify biological markers that might, for example, provide information about a tumor’s aggressiveness or the types of treatments it will respond to. The blood sample might also be used to identify new genetic mutations that increase or decrease breast cancer risk.

A registry study may require you to complete one questionnaire and give one blood sample. Or it may involve completing a series of questionnaires over time. Registry studies that follow people over time allow researchers to identify possible correlations between an action (like exercise) and an outcome (like breast cancer recurrence). Some registry studies are conducted solely online; others require enrollment at a research site. Some registries are established by university- or government-affiliated researchers, while others are organized by non-profits. All provide opportunities to participate in a research study that can advance our understanding of breast cancer.

The Cancer Experience Registry is an example of an online registry study conducted by a nonprofit—in this case the Cancer Support Community. This registry is open to anyone who has had a cancer diagnosis, whether they were diagnosed a week ago, are currently undergoing treatment, or are a long-term survivor. Researchers intend to use the information collected through the Cancer Experience Registry to develop programs that address the emotional and social needs of cancer patients and survivors. Individuals who enroll in the registry are asked questions about their diagnoses, overall health, and the impact cancer and its treatments have had on them physically, financially, socially, and emotionally. By conducting the registry trial completely online, the Cancer Support Community is hoping to reach and glean information from a broad a range of cancer survivors.

The SystHERs Registry (Systematic Therapies for HER2+ Metastatic Breast Cancer Study) is an example of a registry that is enrolling patients at a research site—in this case, 100 research sites nationwide. A group of academic researchers started this registry in order to learn about how doctors in the “real world”—outside of clinical trials—are using the new HER2-targeted treatments in women with HER2+ metastatic breast cancer. The researchers are also asking questions about the side effects patients are developing and collecting information on how the tumor is responding to the treatment.

All of the registry trials listed on BCT can be found here.

December 9, 2014 at 4:53 am Leave a comment

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