Neil Iyengar, MD: That being said, I’d like to get to our cases. I think you have a really interesting case that we’d like to discuss today. Could you go ahead and tell us about your patient?

Milana Dolezal, MD, MSci: My patient originally presented to the hospital. I saw her as a consult in the hospital. She was having pretty profound shortness of breath, to the point where her scans showed SVC [superior vena cava] obstruction. She had a lot of adenopathy, lymph nodes that were swollen in the mediastinum, lymph nodes that were swollen in her neck. I was actually thinking this might be lymphoma or even a type of lung cancer. But then when I did her breast examination and felt underneath her arm in the axilla, she had, unfortunately, a fungating type of breast mass. That was a hint in terms of what we were dealing with. She had systemic imaging, so she had CT scans, bone scans, and then she also had a baseline brain study at that point, with the thinking that this could be a lung cancer possibly as well. She had a biopsy, and this was HER2-positive metastatic breast cancer.

In the hospital, I started her on the CLEOPATRA regimen. She got Taxotere [docetaxel] chemotherapy. She got Herceptin [trastuzumab] and pertuzumab. Unfortunately, she had a Taxotere reaction. We were able to manage that and then switched her taxane therapy and continued that, and it was really remarkable within about 2 cycles. She was in the hospital for almost 3 weeks, so it spanned 2 whole cycles. Concomitantly, she was also diagnosed with hepatitis B and D, which was a bit of a challenge to try and manage her LFTs [liver function tests] and the Taxotere adverse effects. It was rocky, really rocky. But we got her out of the hospital, and within 2 cycles, a lot of the adenopathy started to just melt away. Her SVC syndrome remarkably improved. She didn’t need to have any radiation therapy, because that was an initial consult there, in terms of do we need to act quickly? She responded extremely well, and she had tumor markers CA [cancer antigen] 27, 29, and 15-3 that were through the roof. And her liver enzymes improved remarkably. We were able to transition her to an outpatient pretty quickly, and then continued that regimen for quite a few cycles, about 6 to 9 cycles, where she continued to have resolution of all the lymph nodes and the breast mass shrunk. She was able to manage that as well in terms of wound care, feeling much better, going from a bedbound performance status to being able to participate in her kids’ lives.

She continued that regimen, and then we transitioned her to Herceptin and pertuzumab in the maintenance setting without chemotherapy. That was great because she got all of her hair back and she could participate in birthdays and graduation pictures and stuff like that. She did really well in terms of her systemic control from all those lymph nodes, liver metastases, etc. Unfortunately, the disease came back, and we had been doing MRIs of her brain. Just to segue a bit on that, not at that time, but when we saw that HER2CLIMB data, I have changed my practice in the last 2 years or so by doing MRIs of the brain about every 6 months and/or at any progression. I think arguably if we treat a brain metastasis earlier, we don’t necessarily know how that influences overall survival. And I think that if patients aren’t symptomatic, we could have a different discussion about that with our radiation oncology colleagues. If we’re putting them on a tyrosine kinase inhibitor, like tucatinib, do we wait for that to work if those patients are asymptomatic? Maybe we can pause there for a second and talk a bit about her history and an almost 2-year history of being on a first-line CLEOPATRA-type regimen and in the maintenance setting until unfortunately she developed a brain metastasis. We can talk about how we manage that.

Neil Iyengar, MD: That’s so fascinating. Thank you for sharing, and what a great feature of her history that you were able to get her to family events and so forth. I think the comments you made about screening for brain metastasis are very interesting, as we’ve all thought about how our practice may change. I’ve done the same, I have to say, I’ve started to do more frequent MRIs of the brain. I think that’s largely because, in the past, we simply didn’t have very effective systemic agents for CNS [central nervous system] disease. Now that we do, I feel that we have the rationale to do that screening. I also get brain MRIs now, at least at the time of progression, whenever there’s progression. That can now inform the treatments that we select. The other point that you made was concerning the continued impressive efficacy that we see from CLEOPATRA. This continues to be a long-term efficacious regimen, and particularly once in the maintenance setting, I think that it’s very tolerable for our patients. How long did your patient stay in the maintenance setting, and did you have to add any therapies in that setting to help her?

Milana Dolezal, MD, MSci: She remained on Herceptin and pertuzumab for almost 2 years. It was well over 18 months of being in that phase. Now, this was pre-Phesgo in terms of being able to do a shot. She was coming in for her infusion every 3 weeks and doing, like I said, incredibly well. A comment to your point about MRIs of the brain, I think it’s also really important to do a complete neurologic exam. Sometimes you can pick up little nystagmus or other stuff, even if the patients don’t have headaches. Really screening for headaches or any visual changes, that kind of stuff. She did remarkably well. Then there’s also the other question of if somebody’s tumor markers have normalized, originally, we were staging her every 3 months or so. I wasn’t necessarily checking a brain MRI every 3 months, but there’s that question of, why don’t we space out our scans a little more? Should we do it every 4 months? How comfortable are we with that in terms of following patients whose tumor markers have normalized?

Most of her systemic disease had improved remarkably, to the point where she was almost NED [no evidence of disease] systemically on this maintenance. This patient did have quite a bit of burden of disease, and she didn’t have brain metastases at baseline. But I have had patients come to me who’ve been on maintenance for even 5 years, and maybe they had a solitary bone lesion or 1 area that could have been zapped, and they come to me for the consult of “how long should I be on this for?” I think that’s another question in terms of therapy for life. I think we all have that feeling that you have to continue the therapy. In that particular patient, I ended up doing a baseline brain MRI. Unfortunately, she had asymptomatic brain metastases, which is too bad. She did extremely well, but then unfortunately, she developed brain metastases after brain metastases.

Neil Iyengar, MD: Those were a lot of great points that you raised. I’ll plug that I think the maintenance setting is an area where we are seeing a lot of investigation, and that may evolve in the near future. This is an area that is ripe for the development of novel biomarkers. Certainly, for exceptional responders like your patient, looking at things like circulating tumor DNA and so forth to guide our management are things that are coming down the pipeline. Before we move into the second-line setting, just a reminder to folks that even in the first-line setting, we may see data soon where we challenge what our current paradigm is with DESTINY-Breast09, which is testing trastuzumab-deruxtecan vs trastuzumab-deruxtecan with pertuzumab vs the CLEOPATRA regimen. There is a lot of investigation in this space.

Transcript edited for clarity.