Jamie DePolo: Hello, thanks for listening. Our guest is Brian Wojciechowski, MD, who practices medical oncology in Delaware County, Pennsylvania, at Riddle, Taylor, and Crozer hospitals, and also serves as Breastcancer.org medical adviser. A native of South Philadelphia, he trained at Temple University School of Medicine and Lankenau Medical Center. Dr. Wojciechowski is a sought-after speaker on the topics of medical ethics and the biology of cancer.
At the recent 2022 American Society of Clinical Oncology Annual Meeting, researchers presented results showing Enhertu, which is a type of medicine doctors call an antibody-drug conjugate, improved both progression-free survival and overall survival in people diagnosed with previously treated metastatic HER2-low breast cancer.
Dr. Wojciechowski joins us to explain what HER2-low breast cancer is and what the results could mean for people diagnosed with this type of metastatic disease. Dr. Wojo, welcome to the podcast.
Dr. Brian Wojciechowski: Hey, thanks for having me, Jamie.
Jamie DePolo: So, to start, could you tell us what HER2-low breast cancer is? Because that seemed to be the biggest question that we got after this research came out.
Dr. Brian Wojciechowski: Yes. So, I'm going to assume everyone understands what HER2-positive breast cancer is. I mean, I guess I can explain it. HER2 is a receptor on the surface of some breast cancer cells — about 25% of people with breast cancer will be positive for HER2 — and it's kind of like an on switch to stimulate growth of tumor cells. And if someone has HER2-positive breast cancer, that means that it's a slightly more aggressive cancer, but it also opens up a whole world of different treatments, HER2-targeted treatments like Herceptin.
So, among breast cancers that don't express HER2, there is a subset, a small group, that actually do express low levels of HER2, and the investigators for the drug that we're talking about were hypothesizing that their drug might be able to help those patients.
Jamie DePolo: So, in other words — let me make sure I'm understanding this correctly — the cancer has some HER2 receptors, but not enough to trigger a positive test. So, the test would still come out either negative or borderline, depending on which test was given.
Dr. Brian Wojciechowski: That's exactly right, and these patients, historically, would not have been considered HER2-positive.
Jamie DePolo: Okay, so, they would not be candidates for Herceptin and other anti-HER2 therapies?
Dr. Brian Wojciechowski: Yeah, they're below the threshold where they would benefit from those kinds of therapies.
Jamie DePolo: Okay. And I know in this study, the researchers had a definition of what HER2-low breast cancer was. Is that standard? I mean, is it widely known enough that everybody says, “Okay, this is what HER2-low breast cancer is”?
Dr. Brian Wojciechowski: Well, it's standard now, because this study establishes a new standard of care. So, yeah, it is going to be standard moving forward, and I'm sure that anyone treating cancer patients would be able to get that information.
Jamie DePolo: Now, could you explain to us how Enhertu works and why the researchers thought that it might be effective against HER2-low breast cancer when other anti-HER2 therapies like Herceptin have not been?
Dr. Brian Wojciechowski: Yeah. So, Enhertu is an antibody-drug conjugate, and what that means is that it's an antibody attached to a chemo drug. It's not the first drug of its kind, but the generic name is trastuzumab deruxtecan. So, trastuzumab is Herceptin, which is kind of your oldest HER2 targeted drug, very widely used, but it's not a chemo, it's an antibody. So, it attaches to that HER2 on the surface of cells.
Now, the antibody-drug conjugate part is that Herceptin is attached to a chemo drug called deruxtecan, and it kind of acts like a Trojan horse. So, the Herceptin binds to the surface of the cell and delivers this chemo drug directly into the cell. And when you do it this way, not only does it target the chemo more precisely into the breast cancer cell, but because it's not going to the rest of the body, it allows us to give a chemo drug that's much more powerful than other chemo drugs that would go to the rest of the body because that chemo drug is going directly into the cell.
So, I guess the investigators figured that, well, we can more precisely target the HER2 protein with a very strong chemo drug. Maybe this will work where others failed.
Jamie DePolo: Okay. So, it's almost… I'm going to paraphrase you in my terms to make sure I understand. So, it's almost like a HER2 is almost like a heat-seeking missile, perhaps because it's focusing in on the HER2 receptors, and then it delivers the chemo right to the breast cancer cells.
Dr. Brian Wojciechowski: Yeah, I think that's a great analogy.
Jamie DePolo: Okay. Okay. So, the results of this study, which was called DESTINY-Breast-04, they were so well received at ASCO that Dr. Modi, who was the presenter — I watched the presentation — she got a 40-second standing ovation when she was done. So, obviously, as you said, this is practice-changing. How big are these results?
Dr. Brian Wojciechowski: It's a pretty big deal. I mean, remember, this study was in metastatic disease, and they were comparing their drug not to placebo, but to chemotherapy on the other side. It was investigator's-choice chemotherapy.
And usually when you have that situation, it's pretty easy to show progression-free survival, which is the time it takes the cancer to get worse on treatment. But it's less common to actually see an overall survival benefit, and when you do see overall survival — and overall survival is how long people actually live with the cancer. When you see an overall survival difference, that's considered pretty remarkable, and in this case, the overall survival difference was 23.4 versus 16 months for the whole group.
Yeah, so in the oncology world, we don't see that very often, an eight-month difference, so that was pretty impressive, and yes, I would have clapped for 40 seconds if I was there as well.
Jamie DePolo: Well, that's great. Do we know how many people this might have implications for?
Dr. Brian Wojciechowski: I don't know the percent of women with metastatic breast cancer who are HER2-low, unfortunately, but I can say this at least: that anyone out there with metastatic breast cancer should look at this, and I think their doctors should go back and decide if they're HER2-low or not, and try to use this drug once it gets approved. So, I think really it probably has implications for anyone with metastatic breast cancer.
Jamie DePolo: Okay, well, that's great. That was a great lead-in to my next question because that's what I was wondering. So, if I'm diagnosed with metastatic disease, and my pathology report, the results said the breast cancer was HER2-negative, I should go talk to my doctor and say, “Hey, let's look at the pathology report again, is this really HER2-low that got classified as HER2-negative?”
Dr. Brian Wojciechowski: And that's a very distinct possibility that could be the case. And by the way, it's whether you’re hormone receptor-positive or -negative. So, yeah, I think anyone with metastatic disease should talk to their doctor about this study.
Jamie DePolo: Okay. Is it likely or a possibility that somebody might need additional HER2 testing, or could the results of the original path report be used?
Dr. Brian Wojciechowski: It really depends. I think, in most cases, you can use the results of the original path report, but in some cases, I think rarely, there might be the requirement for another biopsy or to go back and do additional testing on the original report.
Jamie DePolo: Okay. And then finally, I'm assuming the FDA is going to have to change the prescribing indication for Enhertu to include HER2-low metastatic breast cancer, which could take some time, depending on how everything goes and when the application is made. But I guess what I'm wondering, given that it's metastatic disease, if somebody has metastatic HER2-low breast cancer that isn't responding well to other treatments, is it possible that somebody could get this off label?
Dr. Brian Wojciechowski: Yeah. I mean, we do off-label all the time, and it really depends on the insurance carrier. So, you know, I'd probably try it if I had the right patient.
Jamie DePolo: Okay. Now, in your personal experience, have your patients asked you about this? I mean, is there a lot of buzz about it?
Dr. Brian Wojciechowski: Not yet, not in my patient population where I practice, but we'll see. We'll see what happens. I don't know if the word is quite out there yet, which I guess is why we're doing this?
Jamie DePolo: Yes, that's exactly why we're doing this. Yeah, we want to let people know. Thank you so much, Dr. Wojciechowski. I know this has been helpful, and I appreciate your insights.
Dr. Brian Wojciechowski: Alright. Thanks for having me.
