Adam Brufsky, MD, PhD, professor of medicine at university of Pittsburgh, co-director of the Comprehensive Breast Cancer Center of the University of Pittsburgh Medical Center Hillman Cancer Center, talks about a new treatment to improve quality of life for triple negative breast cancer patients.
Can you tell me a little about this new drug called Trodelvy?
BRUFSKY: Yes. It’s also known as sacituzumab govitecan. The trade name is Trodelvy. It is a class of drugs called antibody drug conjugates. What that means is we take an antibody which binds to a protein on the cancer cell and attach chemotherapy to it. It’s kind of like a magic bullet. We take a chemotherapy that otherwise would be very toxic at high doses, and because it’s so targeted just to the cancer cells, we can give it at a lower dose with a lot less toxicity. So, Trodelvy is an antibody against a protein called Trop-2 that’s present on 96 percent of all triple-negative breast cancer. It’s attached to a drug called Exatecan. What it does is delivers the Exatecan to the cells. Those cells are then destroyed, hopefully, by the chemotherapy. The nice thing about this is that it has what’s called a bystander effect. That means it gets there and then is kind of cut off. So, it’s released, but released not only in the cancer cell but outside. The cool thing is because it’s outside, you can kill cancer cells not only to the one that it’s directed to, but cancer cells around it. It kind of amplifies its power by a factor of like 8 or 9 or 10. That’s why we’ve been very excited about it for a long time.
How is it administered?
BRUFSKY: It’s administered intravenously the first and eighth day of a 21-day cycle. There are very few side effects. However, the big side effects that we’ve run into with this drug are diarrhea in some people and a low white count in some people. These are manageable by adjusting the dose and giving various drugs. The one thing we were a little bit surprised about is that it has hair loss. I don’t think we thought it would have hair loss because it was a targeted agent just to the cancer. But apparently there’s enough of the Trop-2 protein in hair follicles that have caused hair loss. Other than that, it’s a very manageable drug and well-tolerated in the vast majority of people it’s been given to.
Even for patients with metastatic disease?
BRUFSKY: The beautiful thing about this drug is that it was targeted at a triple-negative breast cancer that already had progressed through two separate therapies. So, you’d already gone through a first line therapy and had progression, a second line therapy and had progression, and that’s traditionally an area where nothing works. So, we thought, let’s try it. A randomized trial was just completed, one that Jane Ellen participated in. It turns out that it doubled the survival of people, which is unheard of. I mean, clearly I want people to live forever, but doubling survival is a big deal. Anything that really moves the needle in triple-negative breast cancer is a big deal. The women who had this drug, like Jane Ellen, had a median of four to six prior therapies. Even though they had all that therapy, these women did incredibly well.
How long can women be on this treatment?
BRUFSKY: The patient you interviewed has been on it two years. She participated in the original trial and this phase three trial. She thankfully got the drug and not the standard of care, which is just normal chemotherapy. Her disease is stable and hasn’t changed.
I was going to ask if you are seeing shrinkage?
BRUFSKY: Initially I saw shrinkage and now it’s just stable. It’s not doing anything, which is good. I always tell people, with cancer, it’s good to have things not get worse and have you live with them. Yes, we want to get rid of everything, but it’s ok that we don’t. In fact, it can still be that we keep it in its place, so it doesn’t do anything. That’s really important. And that’s what this drug is doing in a lot of people.
This would not be a cure then?
BRUFSKY: It depends on what cure means in cancer and especially in solid tumors. The field of oncology started with the treatment of leukemia. In leukemia, you must get rid of every cell or it’s going to grow back. Now, we’ve kind of gone a little bit further out to what we call solid tumors, tumors of the breast, the lung, the prostate, the colon. I think the cure, if we can even call something a cure, is going to be that we control it for long periods of time kind of like heart disease and diabetes. It’s a disease that we turn into something chronic that you can live with that doesn’t affect your life but is still very serious. We can’t do this for everybody. But the idea in breast cancer is something that I’ve done for 25 years. I’ve tried to turn metastatic disease that’s spread all throughout the body into something we can stop in its tracks, or maybe shrink a little, or maybe get rid of all of it, but make it something you can live with and live your life as best as you can. In the vast majority of people, we can’t do this but that’s our goal.
Can you explain what exactly triple-negative breast cancer is?
BRUFSKY: When you come in with breast cancer, we look at it and try to determine what it’s sensitive to. For example, probably about 50 to 60 percent of breast cancer is what we call estrogen receptor positive. That means female sex hormones in your body still cause it to grow. Even though some women are in menopause, they still have enough estrogen in their body to make it grow. So, we use anti-estrogen therapy in the body with various drugs to kill the estrogen. Then, about 10 or 15 percent of breast cancer is what’s called HER2+. There’s a protein on the cell called HER2 that’s overexpressed. So, we use a monoclonal antibody therapy called Herceptin with chemo and other agents. That’s the cancers that potentially get rid of all of it. I’ve had patients who have what’s called a complete response meaning they have metastatic disease, yet all of their cancer has gone away. It’s a minority, but you still have people with HER2+ that goes away. Triple-negative breast cancer is everything that HER2 is not and not estrogen receptor positive. It’s kind of what we call a diagnosis of exclusion. It means that it doesn’t fit the other two categories. So that’s probably 15 percent of breast cancers that most people see and is very heterogeneous. There are many kinds of triple-negative breast cancer. There’s the kind that’s associated with a gene mutation like BRCA1 or 2. There are therapies called PARP inhibitors, a drug called Lynparza, and another one called Talzenna that we can use. There’s triple-negative breast cancers that are responsive to immunotherapy. About 40 percent of breast cancers have a protein on their surface called PD-1, L1. We can give them immunotherapy. And, this drug, Trodelvy, is one of the new drugs that we can now use for triple-negative breast cancer that we didn’t have in the past.
When did this get FDA approved for clinical trial?
BRUFSKY: It got FDA approved based on an early phase 2 trial. It was around May because they were waiting for the results of this phase 3 trial to be announced. The phase 3 trial did exactly what it was supposed to do. It replicated the phase 2 trial and worked well. It gave us what we didn’t know from the phase 2 trial which was the survival was doubled. That trial just presented at an international virtual meeting in Madrid. And that will hopefully be published in the big journal within the next month or two.
What about Jane Ellen’s cancer and situation made her a good candidate for this trial?
BRUFSKY: Jane Ellen had disease predominantly in her lungs. She didn’t really have a lot but was motivated to do the trial. She is a veterinarian so she’s very scientific and has an understanding of science and medicine. They put her on a trial before that of some immunotherapy and it caused her some problems. So, we took her off that trial and decided to try this. I always tell people for clinical trials, at a minimum, you’re going to get the best therapy we have. You’re not a guinea pig. We don’t put people on placebo controls. Everybody thinks they are not going to get any therapy on a clinical trial. That’s not the case at all. What most people do on a clinical trial is get the standard of care, but it could be the standard of care five years from now. That’s what Jane Ellen received. She got the therapy that is now the standard of care two years in advance and has benefited because of it.
And how is she doing now?
BRUFSKY: Great. The disease is under control and she’s doing really well. I always tell people with cancer, you never know. There’s so much not known about this business and I’ve been doing this long enough to know that. But on the other hand, she’s doing really well and there’s no reason to believe that she won’t continue to do well for the foreseeable future.
Is there anything you would like to add to make sure people know about this treatment?
BRUFSKY: No, not about this treatment. But one thing I will say is that it’s important to continue to get your health screenings. I know we’re in the middle of a pandemic, but you need to keep doing the things you need to do to get health screening. We know people fear getting the virus, but we have social distancing, and we have masks. The hospitals now are extraordinarily safe. The virus should not be a reason to avoid getting that mammogram or going in to get that checkup or if you have heart disease being sure you go see your cardiologist. This pandemic is going to end someday, but it’s important right now to understand you cannot stop your health screenings.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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