Q & A with Dr. Michelle Melisko, MD

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

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.

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Entry filed under: Brain metastases, Breast Cancer Treatment, Metastatic breast cancer, Metastatic breast cancer clinical trials, Metastatic Trial Search. Tags: , , , , , , , , , .

Talking About Metastatic Breast Cancer Trials  Studying New Ways to Treat Brain Metastases

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