Neil Iyengar, MD; Claudine Isaacs, MD; Virginia Kaklamani, MD; and Vijayakrishna Gadi, MD, PhD, share clinical pearls for the evolving treatment landscape of HER+ metastatic breast cancer.
Neil Iyengar, MD: My opinion is, I’m very interested in all of the correlative science that’s going on, because I think that might help guide us in terms of patient selection. I hope that we’ll have some clinically actionable data from some of these completed trials. But beyond that, I think we’re starting to see several of these agents move into potentially earlier and earlier lines of therapy. A lot of our sequencing discussion that we’ve had tonight and that we commonly have with our colleagues, some of those questions, not all, but some of those questions may have more data now to guide the answers. And we may be seeing some of these agents as options in earlier lines. We heard from Dr Kaklamani about potentially T-DXd [trastuzumab deruxtecan]in the second-line setting. We are even seeing trials in the adjuvant and neoadjuvant space. I think that the whole landscape is shifting right now. But I think the major areas of need right now are patient biomarker identification to help guide treatment selection. Then I want to go back to the original point that was made with regard to leptomeningeal disease [LMD]. We still don’t have really good treatment options for our patients with LMD who have been excluded from all of the trials we’ve discussed tonight.
Vijayakrishna Gadi, MD, PhD: There is a trial through the Translational Breast Cancer Research Consortium looking at tucatinib in the LMD population. Hopefully, we’ll have, I doubt it’ll be a complete answer, but at least some sort of answer in that space as well. Something interesting is happening in oncology. What’s the dictum, “If you can’t beat them, join them.” You’re seeing these combinations, we hinted at this a little while ago. Dr Kaklamani, does it worry you that you might have to use tucatinib with trastuzumab deruxtecan? Is that a toxic mess we’re about to create, or do you think we can get by with this?
Virginia Kaklamani, MD: Well, there are clinical trials addressing that, especially in patients with brain metastases. We still won’t know whether it’s better to use one drug versus the other, but we’ll know how well the combination works. I think you’re right; all of these trials are designed to be positive more than they’re designed to answer a realistic question we all are asking in the clinic. We’ve come so far with that, but at the same time, it would be nice for us to have the answers. What is the best sequencing strategy? Is combination really a better approach? Or are we just adding to patient toxicity, and financial toxicity for that matter?
Vijayakrishna Gadi, MD, PhD: I can’t imagine the financial toxicity of combining pertuzumab, trastuzumab deruxtecan, tucatinib, and let’s throw in a checkpoint inhibitor while we’re at it. It could be profound toxicity to the pocketbook as well. With that, we’re at the tail end., I want to give each of you an opportunity to share a clinical pearl, something that everyone can go back to their office with tomorrow and say, “Hey, this is something I might do.” Dr Isaacs, let’s start with you.
Claudine Isaacs, MD: I guess thinking about the importance of neoadjuvant therapy. What I’ve moved to is, I have very few patients for whom I don’t think about giving neoadjuvant therapy in the HER2-positive space. Maybe the patients who have really small tumors, who are node negative. But I think we do not want to lose the ability to adapt our adjuvant therapy based on the response to neoadjuvant therapy. I think the KATHERINE data showed us very clearly that we could change outcome for these patients. And it wasn’t just that crystal ball where we’re telling them, “You have a path CR [pathologic complete response],” or, “Oh, no, I’m so sorry, you don’t.” It really changes things. I think that is a culture shift that we have seen and that I think is critically important in HER2+ disease and triple-negative disease, the importance of neoadjuvant therapy.
Vijayakrishna Gadi, MD, PhD: Thank you. Dr Kaklamani?
Virginia Kaklamani, MD: To your point, some of these patients may not be excellent candidates for a quadruple combination, but just giving them paclitaxel and trastuzumab neoadjuvantly to see what kind of response they get. Because as you mentioned, T-DM1 [trastuzumab emtansine] might be a much better option for them than having given them TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] in the first place. I think this is exciting. The past 2 years and 4 new drugs approved, and we haven’t discussed margetuximab at all because we just now started using it, but we have options for our patients. And this is what I tell our patients, it’s pretty hard to run out of options. For me, this is a great problem to have. The other thing that is going to be emerging probably in the next few years is the HER2-low patients. The patients who have HER2 1+ or 2+ status who are considered HER2-negative, and some of these treatments may be pretty active in this patient population.
Vijayakrishna Gadi, MD, PhD: Then lastly, Dr Iyengar, you get 30 seconds for your pearl.
Neil Iyengar, MD: It’s hard to add to those really wonderful points that were just made. But I’ll say that what I would emphasize is the need, as is possible, to rebiopsy, particularly when we’re in the establishment of metastatic disease space, because we know that clonal evolution can occur. And now that we have all these wonderful treatments for HER2-positive disease, even in the setting of early stage disease that might have been HER2-low or HER2 zero even, I think it’s critical to re-evaluate our patients, and potentially at certain points of progression in the metastatic setting. If our patients are amenable to it, and it’s not too burdensome to them based on the site, we’ve got a lot of great treatment options. We need more data from the patient themselves if it’s not too burdensome to guide that treatment.
Vijayakrishna Gadi, MD, PhD: Dr Iyengar, you stole my pearl, which is to check HER2 all day long. I completely agree with you. We didn’t talk about it much, but the nuance of knowing the amount of HER2 positivity in a tumor specimen may impact my treatment decision. I might be more inclined to go with a drug with good bystander killing, opposed to one that is much more precise and targeted at only HER2 positivity that’s high. I think that’s a really good point. I’ll also add, don’t do immunohistochemistry [IHC] on your metastatic specimens, do FISH [fluorescence in situ hybridization], do something else, because you’re going to sometimes miss it with IHC. That’s a great point. With that, I think we’re done.
I appreciate the attention of the audience. I appreciate my 3 wonderful, esteemed colleagues, people I love working with and sharing, and doing seminars like this with. With that, I’ll let everyone go enjoy their dinners. Thank you.
Vijayakrishna Gadi, MD, PhD: With the last few minutes, I want to go to our wish list section of this seminar. Neil Iyengar, what do you think are some promising developments in the HER2 mBC [metastatic breast cancer] space? What are you looking forward to maybe at the San Antonio Breast Cancer Symposium or ASCO [American Society of Clinical Oncology annual meeting] 2022 or beyond?
Transcript edited for clarity.