Vijayakrishna Gadi, MD, PhD, presents the case of a 63-year-old woman with grade 3 HER+/HR- metastatic breast cancer.
Vijayakrishna Gadi, MD, PhD: Let’s go on to the next polling question, which is, how likely would you be to use tucatinib for third-line therapy in a patient with HER2-positive mBC [metastatic breast cancer] without brain metastases? We have some saying very unlikely and then we have some likely; now they’re balancing out a little bit. So, some spread but most answered with the likely category. Dr Isaacs, is anything there surprising to you in terms of how folks are responding?
Claudine Isaacs, MD: I think we spend a lot of time talking about what we’re going to use, in the second line, third line, or fourth line, but the good news is we’re probably, for most of our patients, going to use all of these drugs. It’s very individual, all of the factors we’ve talked about: patient-related, the other subtleties about what they prefer, do they want oral therapy, how do they want to do things? I think that all comes into play in the decision-making. I think the important thing to remember is that tucatinib was active whether the patient had brain metastases or not, and so I think it’s a perfectly reasonable choice there. It’s also perfectly reasonable to put something else as in the third line and use it as fourth line if you feel that a different regimen, like the T-DXd [trastuzumab deruxtecan] regimen, might be better in that patient population in the third line. I think the spread really reflects that we’re sitting in front of individual patients and making choices between lots of good choices in some ways, something we didn’t have a year and a half ago.
Vijayakrishna Gadi, MD, PhD: The theme is optimization for the patient who’s sitting in front of you. I think the data guide us but, yes.
Let’s go ahead and go on to the second case, and then we’ll talk about this. This is a 63-year-old woman diagnosed with right-sided IDC [invasive ductal carcinoma], stage IIA, T1N1M0, grade 3, hormone receptor-negative/HER2+ by immunohistochemistry. She gets preoperative therapy with TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] x 6, and she also gets a pCR [pathologic complete response]. She goes 36 months but later shows recurrence in the lung and the bone. The biopsy of the lung confirms HER2 positivity, reflective of the original disease. She gets THP [docetaxel, trastuzumab, pertuzumab], gets a PR [partial response]. Eighteen months later, she gets progression in the lung, she gets trastuzumab emtansine, achieves another PR, stable for a couple more months. But then 6 months later, she has even more lung metastases, so continually progressive lung metastases here. How would you treat this patient? What kind of options would we have in this patient with visceral disease in the lung? Dr Iyengar, you’re up.
Neil Iyengar, MD: We’re certainly getting the sense that this patient probably has a little more rapidly growing or aggressive disease, when you would expect a median PFS for T-DM1 [trastuzumab emtansine] to be around 9 months in this setting, so a little short of that. Again, it’s what we talked about earlier in terms of recurring after a neoadjuvant dual anti-HER2 therapy, perhaps not portending so well. That all being said, we now have a lady with visceral disease who is essentially in the third-line setting. I think this gets back to our discussion about what sort of toxicities would guide you, does the metastatic site in terms of visceral disease guide you? We certainly have the tucatinib-based regimen available to us here, we have trastuzumab deruxtecan available to us here. I think that’s probably where most of my thinking here would center. I think the point can be made that trastuzumab deruxtecan, we may reach to for objective reduction in tumor size, particularly in the lung. But we also see visceral responses with a tucatinib-based regimen. And depending on her symptomatology, if I can’t differentiate whether she’s developing early pneumonitis or ILD [interstitial lung disease], that may guide me one way or the other. I don’t think there’s a wrong answer here. I think Dr Isaacs very correctly, nicely stated that these patients are going to get all of these drugs, and how do you sequence that, and also, we’re going to have combination data coming out soon from some of these other ongoing trials. At this point for this patient, I think in terms of efficacy, it would be reasonable to choose trastuzumab deruxtecan or the tucatinib-based regimen and to let the patient sitting in front of you guide that decision.
Vijayakrishna Gadi, MD, PhD: I want to ask a few more questions around this. Dr Kaklamani, you mentioned also this might be a patient where you would elect trastuzumab deruxtecan. Let’s talk about the weight, the quality of the evidence. On the one hand, we always demand that we want OS [overall survival] data, we want OS data, and this and that. It’s always the best thing, and it’s a randomized controlled phase 3 trial, HER2CLIMB, and yet we’ve got this incredibly sexy data with trastuzumab deruxtecan. But the weight of the evidence, if you are critical about it, lies with the HER2CLIMB study. How does that sway your decision-making? How should we incorporate, interpret the NCCN [National Comprehensive Cancer Network] guidelines in this kind of patient?
Virginia Kaklamani, MD: I think you’re right. If you’re a purist, you want to look at a phase 3 trial and say there are a lot more data there compared to a phase 2 clinical trial. But the disease control rate in the phase 2 clinical trial was 97%, and it doesn’t get any better than that. There was 1 patient who did not have some sort of response or stable disease; this is pretty compelling. Have we been burned in the past? Yes, we have, but not with data this compelling. Like Dr Iyengar said, I think you’re not going to be wrong picking either of those 2 agents. You could say that for visceral disease, I’ll give T-DXd [trastuzumab deruxtecan], for brain metastases, I’ll give tucatinib. I want to venture out and say that maybe the blood-brain barrier doesn’t exist in patients with brain metastases to begin with. And as long as you’re using an active agent, you’re going to have responses. We see this with T-DM1 [trastuzumab emtansine], there are data in brain metastases, we see this with the most recent data from T-DXd [trastuzumab deruxtecan], and we see this with the data from tucatinib. Who knows?
Vijayakrishna Gadi, MD, PhD: Thank you. That was a tough question, and I appreciate the honest answer. And it is right, it would take something really surprising to happen for that data to look significantly less good than it does right now. This is a funny patient because we’ve been talking about screening for brain metastases this whole time. She’s had progression, rapid progression. I feel like this is a patient for whom you guys might have snuck in a brain scan already. Dr Isaacs, is that true?
Claudine Isaacs, MD: Yes, I would have done it. At this point, I would have definitely done a brain scan. I agree completely with my colleagues, and I agree completely with Dr Kaklamani, but I think, to give discussion here, the fact is that T-DXd, the trastuzumab deruxtecan data, were in patients who had received a median of 5 to 6 prior lines of therapy. It’s not like you couldn’t give it to that patient after as well. I think the point is, what we’re all saying is that there is no single right answer here. It’s going to depend on the patients for which treatment you do third and which you do fourth in a patient like this. But yes, I would have done a brain scan on that patient. And yes, if she had brain metastases, that would have compelled me to do the tucatinib triplet in that patient, over doing the T-DXd [trastuzumab deruxtecan]. But again, I think these are all right answers. As Dr Iyengar said, there’s no wrong answer here.
Vijayakrishna Gadi, MD, PhD: Thank you.
Transcript edited for clarity.