Adam M. Brufsky, MD, PhD: Welcome to this Targeted Therapy® program entitled, “Conference Review, San Antonio Breast Cancer Symposium 2020.” I’m Dr Adam Brufsky from the University of Pittsburgh, in Pennsylvania, and joining me today in this discussion is my colleague, Dr Erica Hamilton of Sarah Cannon Research Institute, Tennessee Oncology.
Our discussion today is going to focus on the San Antonio Breast Cancer Symposium coming up in December, what the year has brought, and what we hope to see at the conference to help women with breast cancer. Let’s get started.
Let’s start thinking of the last 12 months with approvals for some of the drugs. What do you think are some of the big ones that have been approved, Erica?
Erika P. Hamilton, MD: The biggest story has been probably HER2 [human epidermal growth factor receptor 2]. We had trastuzumab deruxtecan approved about a year ago, in December of 2019, and then tucatinib quickly on its heels. We also had a new drug for triple negative breast cancer, sacituzumab govitecan, and we’ve seen some of the data from that this year as well. It’s been a good year for breast cancer.
Adam M. Brufsky, MD, PhD: I would agree with you. I’m intrigued by the approvals; they were pretty interesting. We’ll get to sacituzumab in a minute, but trastuzumab deruxtecan has a chance to be a total game changer in our business. We’re all excited when they showed us that forest plot or the waterfall plot at the San Antonio [Breast Cancer Symposium] last year. It looked dramatic, but what was even more dramatic was the progression-free survival and the overall survival. The progression-free survival was something like 14 1/2 months, and the overall survival wasn’t reached in people who had a median of 6 regimens for their disease. We’ve got the randomized trial coming up, and we may hopefully see it at ASCO [the American Society of Clinical Oncology annual meeting] in 2021, or somewhere thereabout.
That is something that you don’t see. When you look at all the other trials, you look at tucatinib, which we’ll talk about in a minute because I always use your patient when we talk about tucatinib and what you did. But before we get there, trastuzumab deruxtecan is a big deal, and I’m curious to hear what you think of it.
Erika P. Hamilton, MD: I completely agree. It’s not often that we see curves like that in breast cancer. That reminds me of the TRK [tropomyosin receptor kinase] alteration curve, and we don’t get things like that in breast cancer. That was impressive. You certainly have to feel good putting a patient on a therapy when you’re almost guaranteed that they’re going to get some benefit from it.
Adam M. Brufsky, MD, PhD: I agree with you.
Erika P. Hamilton, MD: You brought up an important point about the duration of response. For how heavily pretreated these patients were, that’s a meaningful response. We’re all getting a bit more familiar with the ILD [interstitial lung disease] or pneumonitis. Pneumonitis was certainly a concern, and it’s still a concern, but it seems to be true that there are more and more drugs across our oncology portfolio for which we’re having to keep a close eye on pneumonitis and caution our patients to let us know if they’re having any symptoms.
Adam M. Brufsky, MD, PhD: I agree. The other big one was tucatinib. The cool thing about tucatinib is that they were really bold in the HER2CLIMB trial. I keep using your patient and what you said about it. You put people on it who had active brain metastases who weren’t getting radiotherapy, and you saw responses. I always use that. You had someone who had a 4-cm lesion. That is great.
Erika P. Hamilton, MD: Before I get a bad rap, that was an exception.
Adam M. Brufsky, MD, PhD: No, it’s not a bad rap at all because the woman had a dramatic response, right?
Erika P. Hamilton, MD: Yes, absolutely. We all have those patients. When somebody asks you about how many patients you have who are actively progressing in the brain, and you say, “a handful,” right? That adds up, especially for people who have already had radiation, and their cancer is growing again. That’s a horrible prognostic situation. To have a drug like this that gets into the brain is meaningful.
The other thing I like about tucatinib is that it doesn’t add a whole lot of toxicity to the backbone with which it’s given: capecitabine and trastuzumab. We certainly see hand-foot syndrome, and we see diarrhea. In my experience, I don’t think tucatinib adds to the diarrhea of what I would expect to see in patients with capecitabine. Some have very little, and some have more; that’s my experience with capecitabine in the clinic as well. You certainly have to watch the liver function enzymes.
With brain metastasis, we’re curing more and more patients who are presenting with early HER2-positive disease, even patients who have had advanced disease, such as node positive disease. For those patients who have cancer that comes back, the new statistic is that up to 50% of them will have brain metastasis at some point. Making sure that we develop great drugs systemically is important, but making sure that we have options for brain metastasis is also important.
Adam M. Brufsky, MD, PhD: I couldn’t agree more. I’ve seen a number of people now in my practice for whom it’s incredible. To think that you have people who progress through the radiation with multiple brain metastases, the scenario used to be that you’d say, “I could reradiate you,” and we all used to do that. We used to give a second course of whole-brain radiation, and you’re now talking about 5000 rad. You’re getting up there. To have something that can give them a decent response—we’re talking 12 months, maybe even longer on average, survival improvements—is a big deal.
Erika P. Hamilton, MD: I agree. I like the data that are also looking at patients who had a CNS [central nervous system] progression event, and they then stayed on therapy after radiation.
Adam M. Brufsky, MD, PhD: I liked that too.
Erika P. Hamilton, MD: They continued to do better than the other arm as well. It’s encouraging us that tucatinib is going to be active for our patients with brain metastasis.
Adam M. Brufsky, MD, PhD: I agree. The last big thing to talk about was the approval of sacituzumab govitecan. This is for a terrible prognosis of disease: people who have been through a third line of triple negative breast cancer treatment. Who survives to that? It’s incredible, and you see a doubling of the survival benefit. The hazard ratio was only 0.47 or something like that. That’s absolutely incredible.
Erika P. Hamilton, MD: Yes, absolutely. Unfortunately, the thing that also stood out to me on that trial was the progression-free survival of what we would consider standard of care chemotherapy.
Adam M. Brufsky, MD, PhD: Yes, that was terrible.
Erika P. Hamilton, MD: These are chemotherapy treatments that we give third-line patients all the time, which have a progression-free survival of 1.6 months. We need better.
Adam M. Brufsky, MD, PhD: We just scanned them, then we’re done, and they progress, right. It has no activity. I agree with you that this will be the new awful baseline that we’ll all be able to use as we figure out where to go next. A lot of people are thinking, there may be some immunosuppression going on. Can we believe it? We’ll be able to use that new baseline when we start to test out all these new drugs in that setting. That was pretty cool.
Transcript edited for clarity.