Dr. Hamilton:
Hello, I'm Dr. Erika Hamilton. I lead the breast cancer research program at Sarah Cannon Research Institute in Nashville, Tennessee.
Graphic: What 2023 drug approvals stand out in your opinion, and how do they each change care?
Dr. Hamilton:
It's a great question. Actually, it's surprising how many drugs were approved in 2023. Some of them seem like a long time ago. We had some advancements in ER-positive breast cancer. Elacestrant (Orserdu), which is a novel oral SERD, is approved for patients who have ESR1 mutations. Which, depending on the setting, can be about 40% of our patients with ER-positive metastatic disease. This is really exciting because we haven't had any new endocrine backbone since the 1990s with fulvestrant (Faslodex), so this is really a huge advance.
The other advance in metastatic ER-positive breast cancer has been the addition of capivasertib (Truqap). This is actually given in combination with fulvestrant, one of our older endocrine backbones. This is in the second-line setting, and what's exciting about this drug is not only does it get PI3 kinase mutations, but also AKT mutations, and other mutations in that pathway. What's exciting is that capivasertib is much better tolerated than even alpelisib (Piqray). Alpelisib can have a lot of hyperglycemia, rash, and diarrhea. So capivasertib is an option for patients who have ulcerations in that pathway that are better tolerated.
Another advance for metastatic breast cancer has been sacituzumab govitecan (Trodelvy), or an antibody-drug conjugate. Sacituzumab is exciting because unlike trastuzumab deruxtecan (Enhertu), you don't have to have expression of the Trop2 protein to be a candidate for this. So it's for all comers, and it really goes across traditional disease settings, ER-positive as well as triple-negative breast cancer.
Then, finally, one of our big advancements in early-stage disease has been a little bit of refining the abemaciclib (Verzenio) label. Abemaciclib is approved for patients that have ER-positive node-positive high-risk breast cancer, and it used to be linked to this diagnostic Ki-67, but it no longer requires a Ki-67 approval now. It's very exciting, and this really can translate more patients to cure. Every time we look at this data at two years, three years, and now, four years, the magnitude of benefit is widening. So we're translating more patients to cure with high-risk early breast cancer.
Graphic: If a patient thinks they're eligible for one of these drugs, what should they do?
Dr. Hamilton:
So the great news about these four drugs is that they're all FDA-approved, meaning you can get this at your local oncologist's office. The easiest thing to do is task "Hey, I think that I may be eligible for sacituzumab govitecan. Do you think so? Do you think it would be a good drug for me?" And I always encourage people to get second opinions as well. Sometimes another look comes up with a new idea, so we always encourage that, as oncologists, as well. Then, even for people who don't qualify for these drugs, there are a lot of great clinical trials out there. Remember that all of these drugs got approved through clinical trials in the past couple of years, and so this is very exciting, and another way for patients to be able to expand the drugs that they qualify for.
Graphic: Are there any hot topics being discussed at SABCS that you're particularly interested in?
Dr. Hamilton:
I think one of the really exciting topics is something that's a little bit surprising. We saw two abstracts, and we first started seeing some data at ESMO. Here at San Antonio Breast, we saw two abstracts about using immunotherapy in patients who have ER-positive early breast cancer. These tend to be patients who are at much higher risk, have lower ER expression, very advanced disease, node positivity, et cetera.
So to think about maybe having immunotherapy for patients who are ER-positive is quite exciting. This is not FDA-approved now. We have seen improvements in pathologic complete response, meaning patients who receive immunotherapy with their chemotherapy, when they go to surgery, are more likely to have no residual tumor left.
We haven't seen this translate to event-free survival. This is an endpoint that takes a little bit longer in the clinical trial, so translates to how many people have their cancer come back. Certainly, we're seeing more data that, for a subset of high-risk ER-positive breast cancer, immunotherapy may be able to improve outcomes.
