Sara M. Tolaney, MD, MPH

 What are the studies on HER2+ breast cancer—during any stage and any location— that you're most excited to see in the next year or so come out? Bill, what do you think is going to be most practice changing, potentially?

 The cases we were discussing early on about early-stage disease and the potential for de-escalation in specific subsets of patients who get a PCR [pathologic complete response], and the flip side of that for those patients who don't achieve a PCR, will drugs—like adding tucatinib—make a difference? Or, as Sara [Tolaney] was mentioning, all of these drugs have a tendency to move up when you've validated their activity in metastatic disease. A number of these trials are now looking at use in the residual disease setting and the neoadjuvant setting; we are at the cusp of learning how to optimally use all of these drugs. The challenge is, as these drugs get moved up for those patients who recur, we're going to have to have something available for them, which again, highlights the reason that there's still so much active drug development in this area.

 Absolutely. Sara, what about you? What are you most excited to see?

 It is exactly what Bill is saying. Can we take these really active drugs and help cure more patients? Can we take T-DXd [trastuzumab deruxtecan], for example, and will DESTINY-Breast05 show that, in residual disease patients, it's helping prevent recurrence? So can we take those high-risk people and do even better than T-DM1 [trastuzumab emtansine] has been doing for people with residual disease? Can we even replace preoperative therapy? I think there are 2 extremes: there's the one that deescalates, like CompassHER2-pCR and Decrescendo to THP [docetaxel, trastuzumab, pertuzumab], and there's the other extreme of taking the really high-risk people and giving T-DXd in the preoperative setting to potentially cure those people. The most exciting thing is being able to cure more patients. I think we've made big strides already with introduction of things like pertuzumab and T-DM1, but now I think there's this opportunity of “right-size therapy;” give people who can get away with less, less therapy, so that they achieve great outcomes with less toxicities, but take people who need more. Now we have all these great drugs and give them more and help cure them. It's a really great time to have all these opportunities for patients.

 I would just dovetail on that and say it's phenomenal the percentage of patients we're now seeing with complete responses in a more heavily pretreated setting with the use of T-DXd. My hope is that we're going to begin to follow these patients who have had a CR [complete response] out and see if we can potentially have long-term durable remission, or even cure in the metastatic setting for select patients. That's an area I think we should focus on. We must keep in mind that 1 of the original patients that Dr Dennis Slamon, director, clinical/translational research at UCLA in Los Angeles, treated with trastuzumab in the phase 1 study was cured of her disease, and she had lung metastases. There are some of those patients who can come off therapy, and that's an area we haven't even begun to address or consider, but hopefully, we'll have the luxury of being able to do that as we have more and more active agents.

I'd like to thank my panelists for a very robust and thoughtful discussion today; you made my job so easy. This is such an exciting area, and having the 2 of you experts really talk about the state of the field right now and where we might be going has been a treat. To our viewing audience, thank you for joining us for this 

Targeted Oncology™ Virtual Tumor Board®

 presentation. We hope today's discussion was a valuable use of your time, and that you acquired practical knowledge that can help you in your clinical practice. Thank you so much.

Videos

Before closing out their discussion on HER2+ breast cancer, expert oncologists share excitement for emerging treatment strategies and ongoing clinical trials. 

Emerging Treatment Approaches in HER2+ Breast Cancer

 Bill, take us through very briefly the CNS [central nervous system] subanalyses from 3 or 4 clinical trials. First, the HER2CLIMB study. What were the intracranial responses and outcomes for patients on that trial? Then we can discuss the DESTINY-Breast03 trial. We’ve danced around it a little today, but maybe you could go through some of the numbers.

 If you look at the HER2CLIMB regimen, tucatinib-trastuzumab-capecitabine vs capecitabine-trastuzumab, the intracranial response rate was significantly higher in patients who received the addition of tucatinib. Most of those responses were partial, but to put it in perspective, it was 41% vs 15%—a fairly dramatic improvement in objective response rate. For patients who did get a response, the duration of that response was double, so it went from 3 months to 6.8 months; that’s meaningful. Have we cured brain metastases? No, but clearly, our response rate has improved dramatically.

If you look at DESTINY-Breast03, the patients who received T-DXd [trastuzumab deruxtecan] compared with T-DM1 [trastuzumab emtansine]: the objective response rate was more than double. These numbers are small; you’re talking about 20 patients in each treatment arm. Nonetheless, it went from 33% to 63%; that’s intracranial response. There’s evidence even though we don’t have a huge trial showing that this has some impact on the CNS.

Similarly, we haven’t talked a lot about neratinib, which is another TKI [tyrosine kinase inhibitor] option at some point in patients with progressive metastatic disease. I’d be more inclined to use that after T-DXd [trastuzumab deruxtecan], but we have evidence from the NALA trial that some patients respond. The partial response rate was similar between those getting lapatinib and neratinib, roughly around 36% to 38%. There was a patient who had a complete response in the brain, and a significant fraction of patients maintained stable disease.

If you look at objective response rate in the brain, it’s about 10% higher in patients who receive neratinib. We have several agents. Back in the day, we did not have a lot; we had anecdotes. Now we’re starting to develop a series of trials that more convincingly demonstrate the efficacy of these drugs in the CNS. The NCCN [National Comprehensive Cancer Network] Guidelines have highlighted this in patients who have brain metastases: we have a number of treatment options that could be chosen. The most compelling data category 1 remains the HER2CLIMB regimen with tucatinib, but we have data with T-DXd [trastuzumab deruxtecan], T-DM1 [trastuzumab emtansine], capecitabine as monotherapy, or capecitabine combined with a TKI such as lapatinib or neratinib. The field is evolving.

 It certainly is. It’s going to be very exciting to see. Given that up to half of our patients with 

 [human epidermal growth factor receptor 2]–positive advanced disease will experience CNS metastases in their lifetime, it’s an area of unmet need. Our screening practices and our management practices are going to change.

Sara, I want to follow on 1 point that Bill made about using neratinib after tucatinib, or not having data to tell us how to sequence these. Have you in your own practice used neratinib or lapatinib after tucatinib or vice versa? These are all TKIs. When you have a patient sitting before you, who’s gone through multiple lines of therapies, sometimes we’ll use similar targeted agents. What’s been your experience?

 That’s a good question. They are different because tucatinib is a more HER2-specific TKI. It’s a reversible inhibitor, whereas neratinib is a pan-HER TKI and an irreversible inhibitor. One could imagine there could be differences. Maybe neratinib, for example, could work post-tucatinib. But as Bill pointed out, but we don’t have data about that. The capecitabine-tucatinib-trastuzumab regimen has survival benefit, but NALA did not have survival benefit. We’ve been preferring to use tucatinib, and it’s generally better tolerated.

Have I ever done it? There was 1 patient that I had done it in because we have a trial ongoing, looking at neratinib in the current CNS trial, looking at T-DM1 [trastuzumab emtansine] with neratinib. Years ago I had a patient who was on the study and then progressed. When the HER2CLIMB regimen became available, she’d experienced further CNS progression but hadn’t seen capecitabine, so she did get capecitabine-tucatinib-trastuzumab. She did have some benefit, but it’s hard to know if it was tucatinib driven because trastuzumab can have benefit as well. It’s an important question that needs to be addressed.

 Those are good points. In our clinical practice, we’ll do therapies such as switching and sequencing therapies in the absence of data, but these studies are going to be critically important in helping guide our practice. What other studies are you excited to see in terms of 

+ breast cancer brain metastases? Are there any studies or drugs you’re following very closely? Bill, you mentioned T-DXd [trastuzumab deruxtecan] earlier. It there anything else that’s exciting to you?

 There are several drugs in development, other antibody-drug conjugates [ADCs]—not just for 

+ diseases. That’s quite an exciting arena. There are of course, several therapies being combined with either immunotherapy or other targeted therapies and even novelty in how the drugs are being designed with regard to the antibody, including bispecific antibodies targeting more than 1 target simultaneously. Even though we’ve made enormous strides, the promise of some of these new drugs makes the future that much more exciting.

 Sara, what are you looking forward to seeing in terms of breast cancer, brain metastases, and ongoing clinical trials? You’ve heard about novel agents.

 Even with T-DXd [trastuzumab deruxtecan], we still have a lot to learn. We’ve seen a little data from TUXEDO-1 with a high initial response rate in the CNS at an interim. We’ve seen a cohort from DEBBRAH presented with about a 50% CNS response. We’ve seen some case series, but we don’t have a large data set. We’ll see more work from TUXEDO and DEBBRAH, but DESTINY-Breast12 will have many patients with CNS involvement that we’d all love to see cleaner data for and large numbers of patients with progressive brain metastases. That will be important to understand. It will be interesting to see how T-DXd [trastuzumab deruxtecan] plus tucatinib performs.

There’s that ongoing trial that you alluded to that allows for patients with progressive brain metastases; it will be interesting to see how that performs with that robust combination. There are other novel agents. We have a few CNS trials ongoing. One is looking at a Zion [Pharma] agent, a TKI, that has good CNS penetration. There are a lot of other agents. There are other ADCs. ARX788 is 1 you’ve been very involved in with development. There’s a study in China for people with progressive CNS disease. There will be lots of new data that will come out, which will be great.

A broad review of CNS-related clinical trial data in the setting of HER2+ breast cancer and concurrent brain metastases.

Case 3: CNS Data From Clinical Trials in HER2+ BC

 This patient gets SRS [stereotactic radiosurgery] to the brain metastases and does change to tucatinib-capecitabine-trastuzumab because her disease is progressing in the lung and brain. She achieves a partial response in the lung, as well as central nervous system responding very nicely. A year later, however, she has new lung metastases, which are leading her to have a cough. Her brain shows stable disease and no new lesions. Sara, how would you approach this patient who’s had stable disease in the brain but is progressing outside the brain and is on the tucatinib-based regimen? How do you choose among the therapies?

 In this case, she hadn’t had T-DXd [trastuzumab deruxtecan]. We gave her THP [docetaxel, trastuzumab, pertuzumab], and she went straight to tucatinib. This is where T-DXd [trastuzumab deruxtecan] comes into play because she’s got systemic progression and stable CNS [central nervous system] disease. You did smartly throw in the issue that she’s got symptomatic lung disease and a cough. But as Bill pointed out, this is the exact patient that needs a response in the lungs to clinically improve. Therefore, I’d feel comfortable using T-DXd [trastuzumab deruxtecan] here.

 Bill, if this patient was stable in the lungs and progressing in the brain on tucatinib-capecitabine-trastuzumab, what would you do?

 It would depend on what prior therapy the patient had to the brain. The fact that systemic therapy is well-controlled gets back to the question of whether radiation—in the form of additional SRS or whole brain—might be the preferred therapy. I’d be inclined to talk to my radiation oncologist before jettisoning the treatment plan that seems to be holding the systemic disease stable.

 Excellent. Sara, when do you bring surgeons into the discussion? Are they involved in the multidisciplinary management of brain metastases from the outset? Is there a tumor board?

 Yes, for all our brain metastases cases, we have a tumor board that does review the cases with surgery and radiation oncology, but the surgical piece comes in certain situations. One is when there’s such bulky disease that you have midline shift. If you’ve got an occluded ventricle or a high ICP [increased intracranial pressure], those are situations where surgical intervention becomes unquestionable—it’s at a critical point where you must intervene. Sometimes, when you have just 1 brain metastasis, this issue comes up. Is it worth resecting oligometastatic disease if that’s the case? Is there survival benefit from doing surgical intervention? At this point it’s hard to know because we’re so good at doing really focal SRS. Sometimes we consider surgery and radiation in those rare oligometastatic cases where there’s no other anatomic reason they need surgery.

A brief discussion on treatment options available for patients with HER2+ metastatic breast cancer and brain metastases who progress on the HER2CLIMB regimen.

Case 3: HER2+ mBC Treatment After Progression on the HER2CLIMB Regimen 

 Let’s go on to our third and final case, which is relating to a patient who does have brain metastases and 

 [human epidermal growth factor receptor 2]–positive disease. We have a 62-year-old woman who presents with a palpable 3.5-cm mass in her right breast, in her right upper quadrant, in her axilla. A core needle biopsy of both areas demonstrates grade 3 IDC [invasive ductal carcinoma], ER [estrogen receptor]–negative, PR-negative, HER2+. Imaging shows a 3.1-cm lesion in the breast, with multiple axillary lymph nodes and 3 lesions in the right lung. Again: de novo metastases. Brain MRI is negative at the baseline. A biopsy of the lung does confirm the same: HER2+ disease. Her performance status is outstanding. She initiates THP [docetaxel, trastuzumab, pertuzumab] for 6 cycles, then goes on to maintenance HP [trastuzumab, pertuzumab]. She’s had a CR [complete response] in the breast mass axilla and lung metastases—a very good outcome. Before I go on to the next slide, are either of you doing brain imaging in patients at their first diagnosis of metastatic disease if they don’t have neurological symptoms?

 Outside a clinical trial, no, we haven’t been. In general, I’ve been scanning with symptoms, but there are a lot of trials ongoing. We have a trial looking to see if screening for brain metastases could have potential benefit. In this case, a trial is designed to see if it will help prevent neurological symptoms by finding those lesions early and potentially intervening early. It’s an excellent question, and it’s unclear what the right answer is here.

 Eighteen months later, she progresses in the lung with 2 new lesions, and she’s been developing regular headaches for the past month or so. At that time she undergoes a brain MRI, which showed 3 brain lesions, the largest being 1.1 cm. The question becomes, how do we treat now? What do we do for this patient? Before we go into what she had, Bill, how would you approach clinical decision-making in this patient?

 Clearly, this patient’s course of therapy needs to change. This morning I saw somebody who had 17 brain metastases treated with SRS [stereotactic radiosurgery]. You wouldn’t have thought beyond 1 or 2 in the old days, but now the sky is the limit. That said, this patient would be considered for SRS. We would try to hold off on whole-brain radiation therapy for these downstream consequences of that for as long as we could. This is a patient with active lung disease, so something going on below the neck and in the head might make the HER2CLIMB regimen more attractive. If she got SRS for whatever reason, T-DXd [trastuzumab deruxtecan] could still be a consideration; it’s not an absolute if SRS is done.

 Let me push you on that a little, Bill. If she came to you and said, “I don’t want to do radiation at this point. Is there any way I can switch my therapy and follow the brain?” Is this the type of patient for whom you’d consider treating her just the change in systemic therapy and initiating tucatinib-based treatment?

 If that were the scenario and the patient was adamant—“I don’t want radiation. I want everything upstairs intact. I want no diminution in my cognitive function, and it’s an absolute—then the most compelling data, particularly for active brain metastases in the HER2CLIMB regimen, are with tucatinib. The data are more compelling based on what we have for tucatinib-based regimens for active brain metastases than T-DXd [trastuzumab deruxtecan].

 Sara, would you suggest she had SRS and then change her therapy? Or would you suggest just changing therapy in this type of patient?

 It’s tricky. It would be a discussion with the neuroradiation oncologist to understand how easy it is to SRS all lesions, how big each 1 is, or how much peritumoral edema is there. You’d want to understand the case in detail to make that decision. In general, I tend to want to SRS the lesions and move on to systemic therapy. It makes me feel as though I’ve got them controlled and I can move on. I tend to want to avoid whole-brain radiation because there are more neurocognitive effects there. If I had an alternative, I’d try tucatinib. In this case, you could have gone either way. If you’re going to do SRS anyway, you could have SRS and gone to T-DXd [trastuzumab deruxtecan] or potentially to tucatinib.

 Multidisciplinary team gets involved as soon as we see brain metastases develop. You’ve both made good points about involving them in the decision-making. I want to change the scenario a little. Bill, let’s assume her lung is perfectly controlled. She’s progressed in the brain, and she’s on HP [trastuzumab, pertuzumab] maintenance. What are your thoughts about changing systemic therapy if the extracranial disease is controlled and her disease is progressing in the brain only?

 This is a tough question because if her systemic disease has been stable for an extended period, I still may approach this patient with SRS and watch carefully for things going on below the neck. I don’t know that I’d absolutely change therapy in that kind of patient. That’s how I’d approach it, but it’s a bit of an unknown. This could be a patient for whom you maintain the current systemic therapy: treat the brain, and watch.

One other thing: when we were talking about ILD [interstitial lung disease] and T-DXd [trastuzumab deruxtecan]. From a compliance standpoint, you have to assess the patient with respect to 3 drugs. The trastuzumab we’re giving to them, but capecitabine and tucatinib are oral medications that you must be confident the patient is taking appropriately.

 Taking 1 continuously and taking 1 for 14 days on, 7 days off so it becomes a lot more complex. That’s a great point.

Centering discussion on a patient case of HER2+ breast cancer with brain metastases, experts consider optimal treatment regimens in this setting.

Case 3: Selecting Therapy For HER2+ Breast Cancer With Brain Metastases 

 Bill, I’m hoping you can take us through a discussion on how to sort through the next line of therapy for this patient when her disease progresses on T-DXd [trastuzumab deruxtecan] based on what we have available. Can you take us through the data? Particularly as it relates to tucatinib, trastuzumab, and capecitabine? Of course, we don’t have data to support the use of T-DM1 [trastuzumab emtansine] after T-DXd [trastuzumab deruxtecan], but we still have this drug available. Can you talk us through the HER2CLIMB study and how you would approach a patient after T-DXd [trastuzumab deruxtecan] and THP [docetaxel, trastuzumab, pertuzumab]? 

 The reality is that we have a lot of options. That’s the luxury in this space for 

 [human epidermal growth factor receptor 2]–positive disease. On the flip side, what we don’t have is a lot of data substantiating a particular sequence as being optimal. That said, after T-DXd [trastuzumab deruxtecan] progression, for most patients we typically think about the tucatinib-based regimen—a regimen that has a survival advantage that has been demonstrated. Data in those with CNS [central nervous system] disease were also enhanced, not only as PFS [progression-free survival] but also CNS [central nervous system] PFS. That would be an attractive next option for patients. It has been clearly demonstrated in that trial that with the addition of tucatinib, trastuzumab, and capecitabine, you improve median overall survival in the population as a whole. It didn’t matter whether you had visceral metastases or no visceral metastases: there’s a substantial clinically meaningful improvement and outcome.

When you think about all the other options, we have some old-school options, including things like an alternative TKI [tyrosine kinase inhibitor] like lapatinib, which I probably wouldn’t opt for. We have a variety of chemotherapy drugs that can be partnered with trastuzumab. These are options that will be exercised further down the line. We even have drugs like newer anti-HER2-directed agents, like margetuximab, which may have a role in later lines of therapy. For most patients, I’d probably opt for tucatinib after T-DXd [trastuzumab deruxtecan]. As you pointed out, 1 strategy that folks like us might say is, “I’d like to come at the tumor with some other drug that has a different mechanism of action.” In other words, T-DM1 [trastuzumab emtansine] is another antibody-drug conjugate [ADC]. It might have the same level of efficacy or be muted after having T-DXd [trastuzumab deruxtecan]. I don’t think we know the answer to that, but my inclination is to try tucatinib before T-DM1 [trastuzumab emtansine].

 Absolutely. What about you, Sara? Do you think tucatinib is the next go-to regimen outside enrolling the patient in a clinical trial, of which there are many? What would be your standard option after T-DXd [trastuzumab deruxtecan]?

 We’re torn between the tucatinib-based regimen or T-DM1 [trastuzumab emtansine] because we don’t have data for anything after T-DXd [trastuzumab deruxtecan] to know what the efficacy of anything is. I was disappointed by the performance of T-DM1 [trastuzumab emtansine] as the control arm in DB03 [DESTINY-Breast03 trial]. The PFS wasn’t what I was hoping it would be, so I’d probably go a bit more toward tucatinib-based treatment. I’m also very curious to better understand how these ADCs perform 1 after the other. They have different payloads, so it’s not that you necessarily expect cross resistance, but I wonder if using an ADC could potentially downregulate HER2 expression. It makes you wonder if another ADC will sequentially work right away. Our group [at Dana-Farber Cancer Institute] has an ongoing biopsy study trying to understand how ADCs function after one another because that’s a big question ; it could go either way. If they had brain metastases, you’d probably prefer giving tucatinib. If they didn’t, you could choose between T-DM1 [trastuzumab emtansine] and tucatinib-based treatment. We’re without data to guide us. 

 We have several ongoing studies looking at T-DXd [trastuzumab deruxtecan] or T-DM1 [trastuzumab emtansine] in combination with tucatinib, so we’ll have more evidence in the coming months and years on how to best partner tucatinib. It could be that the combination with trastuzumab and capecitabine isn’t the ideal partner, but we’ll have to see the toxicity. What’s your experience with the toxicity of this regimen with tucatinib, Bill? Are you seeing a lot of diarrhea in your patients, hand-foot syndrome?

 Not so much hand-foot [syndrome], but diarrhea is what we’ve seen more of. The recommendation should be to tweak the capecitabine dose rather than the tucatinib dose. With that done, most patients are able to stay on it, but diarrhea is something we’ve seen, particularly at the outset. 

 Sara, has the COVID-19 era changed how you’re preferentially sequencing drugs? Are you choosing oral regimens preferentially over IV [intravenous] formulations? Of course, the HER2CLIMB regimen does involve IV, but you can now get subcutaneous trastuzumab and make the visits quick. How has that affected your treatment recommendations? 

 I’ll be honest: it hasn’t influenced it. The patients are still coming in every 3 weeks. If it were T-DM1 [trastuzumab emtansine] or capecitabine-tucatinib-trastuzumab, the frequency of visits to clinic would be the same. It’s nice when you use the subcutaneous receptor formulation, which is what we typically do when someone is getting, for example, capecitabine-based therapy or something oral. In addition, it’s nice for them to pop in for their subcutaneous and be able to get it as an infusion, but it’s not changing that they need a visit, so I haven’t made decisions based on that. 

 Last question on this patient: is there any patient for whom you’d choose tucatinib- capecitabine-trastuzumab before T-DXd [trastuzumab deruxtecan]? The FDA has approved tucatinib in the second-line setting for select patients. Is there a patient for whom you’d change the order and use T-DXd [trastuzumab deruxtecan] after tucatinib, Bill?

 The patient who has dominant CNS disease—that’s the big issue. For that patient, based on the data we have, I’m more convinced about the efficacy of the HER2CLIMB regimen with tucatinib. Our whole way of thinking about big molecules getting into the CNS is probably changing. We may find that for patients even with active CNS disease, T-DXd [trastuzumab deruxtecan] may work fine. We don’t have sufficient data at this point to make that claim. It would be that kind of patient. For somebody who clearly has underlying contraindications to getting T-DXd [trastuzumab deruxtecan] with preexisting pneumonitis of some sort, that would be the patient for whom I’d avoid it. 

 Very much. I like the way you describe it, Bill: dominant disease. That’s good. It’s a little tricky because you could think of someone who had treated stable brain metastases. You could go to T-DXd [trastuzumab deruxtecan] because certainly in DB03, that group of people did very well. Let’s say you had someone who had multiple brain metastases and who couldn’t get SRS [stereotactic radiosurgery]. I had this come up, and I chose not to give whole-brain radiation. I gave them capecitabine-tucatinib-trastuzumab as their second-line approach to try to avoid whole-brain radiation, knowing that this population has very nice CNS response. As you pointed out, there are good survival benefits. This is mostly for the brain-dominant patient. That’s a good way to describe it.

Focusing on the HER2CLIMB regimen, experts consider appropriate treatment options for patients with HER2+ metastatic breast cancer in the third-line setting and beyond.

Case 2: Third-Line Therapy and Beyond in HER2+ Metastatic Breast Cancer 

 This patient did receive trastuzumab deruxtecan [T-DXd]. Remember, she had THP [docetaxel, trastuzumab, pertuzumab] induction for her de novo disease, had a great response lasting 18 months, progressed in the liver, and now she’s had T-DXd, with a partial response in both the breast mass as well as the liver lesions. We’ve talked a lot now about the toxicity of this therapy. I want to hear what your experience has been on a personal level with your patients with this drug. What have you noted in the clinic, Bill?

 Most of our patients have responded; I can’t think of anybody who did not. I haven’t had anybody who had any significant ILD [interstitial lung disease] to date, and I think I’m seeing responses in those with CNS [central nervous system] disease as well. You mentioned the data with stable brain metastases, but there are data with some patients with active brain metastases as well. I think it is a very active drug. To date the toxicity that our group has seen has been modest, but we’re vigilant in looking for it and being sensitive to it. It inevitably will stop working, but to date it’s been a very active, very good drug.

 It’s amazing to see the responses with this drug. When the drug first got FDA approved based on DB01 [DESTINY-Breast01 trial], we were using it in very late-line patients because there had been patients who didn’t have access to it until they had been through multiple lines of therapy. These are people who were progressing through several lines, and then all of a sudden had home run responses as their 7th or 8th line of therapy. It was unreal, and now it’s so nice to be able to use it earlier. The trick that we have learned though is that it does cause nausea for many people, so we do give prophylactic antiemetics with each dose. Some people are using Decadron, Aloxi, and Emend; some people can get away with just Decadron and Aloxi. Then some people need to use Zofran, even in week 2 and 3, there’s this delayed nausea that can happen. That has been helpful to many people to have access to that. We do sometimes see some hair thinning as you pointed out. I too have not had anyone go bald, but it is about a 10% rate of grade 2 that’s been noted with this agent. We don’t know if scalp cooling works, we have a trial ongoing at our institution [Dana-Farber Cancer Institute] looking at that, so we’ll see if that helps. But again it’s generally well tolerated, just some fatigue, nausea; those are the main symptoms I tend to notice.

 There are a lot of eyes on your data relating to the scalp cooling. We’re all waiting to see how that pans out with something that has a longer half-life. One wonders if it’s going to work, but we’re all hoping that in some way it will help.

Expert oncologists share brief notes on their real-world experience managing HER2+ metastatic breast cancer with trastuzumab deruxtecan. 

Sara M. Tolaney, MD, MPH | Authors

Articles

Emerging Treatment Approaches in HER2+ Breast Cancer

Case 3: CNS Data From Clinical Trials in HER2+ BC

Case 3: HER2+ mBC Treatment After Progression on the HER2CLIMB Regimen

Case 3: Selecting Therapy For HER2+ Breast Cancer With Brain Metastases

Case 2: Third-Line Therapy and Beyond in HER2+ Metastatic Breast Cancer

Case 2: Clinical Experience With Trastuzumab Deruxtecan in HER2+ mBC