Neil Iyengar, MD, leads the discussion on the current standard of care and the sequencing of therapy for HER2+ metastatic breast cancer.
Vijayakrishna Gadi, MD, PhD: Hello everyone. My name is V.K. Gadi and welcome tonight to Around the Practice, “Updates on HER2-Positive Breast Cancer.” I am your moderator speaking to you from Chicago, Illinois. I am a professor of medicine and director of medical oncology at the University of Illinois in Chicago. Joining me today are 3 esteemed colleagues, first with Dr Neil Iyengar, an associate professor, newly minted of course, medical oncologist at the Memorial Sloan Kettering Cancer Center in New York; Dr Claudine Isaacs, professor, leader of the clinical breast cancer program, and associate director for clinical research at the Lombardi Cancer Center in Washington DC; and finally Dr Virginia Kaklamani, professor and director of the breast cancer program at UT Health San Antonio MD Anderson Cancer Center. Today, we’re going to discuss some recent data presented at the ASCO [American Society of Clinical Oncology] 2021 annual meeting and talk about some challenges and the treatment of patients with HER2-positive metastatic breast cancer. We will also review 2 patient cases and involve our audience by using an interactive online platform to answer several polling questions that will be discussed by our panelists. Without further delay, let’s began. We’re going to start first with a polling question, if we can bring that up please. Question 1, what is your specialty? a. general medical oncology, b. gynecologic oncology, c. breast oncology, d. radiation oncology, e. other. It looks like most everybody here has checked other, 60% of the folks; 20% of the folks are general medical oncology. It’s now 75% other, 12.5% medical oncology, and I don’t see what answer c. was anymore.
Neil Iyengar, MD: Looks like breast oncology.
Vijayakrishna Gadi, MD, PhD: Breast oncology. Got it. Thank you very much for that. I think we’ve got it figured out now. We will be able to go the next question. Approximately what percentage of your patients have HER2-positive metastatic breast cancer? a. less than 10%, b. 11% to 20%, c. 21% to 30%, d. 31% to 40%, e. greater than 50%. There are the answers. About 37% of you are in the 10% category, 12.5% of you between 11% and 20%, 12.5% of you between 21% and 30%, 25% of you seeing 31% to 40%, and about an eighth of us with high volume of greater than 50%. That helps set the stage and thank you for that. Now that we have got the wheels greased on this, let’s go ahead and jump into the panel discussion. I’m going to do a round-robin style with my esteemed colleagues here. We’ll start with the first question, which is an overview of the standard of care in HER2-positive metastatic breast cancer. Dr Iyengar, I’ll start with you. Maybe you can tell me your overall general approach, lines of therapy, and then we’ll move forward from there.
Neil Iyengar, MD: Sure. I think this is interesting because if we look right on the slide, we see a lot of the recent trials that have made novel agents available to us through 4 FDA approvals over the last 2 years. Certainly the landscape in metastatic HER2+ breast cancer has largely changed. Very generally speaking, because I don’t want to monopolize the conversation, I’ll give a quick run through of how I think about lines of therapy. I think a lot of us are using neoadjuvant therapy in the early stage space, partly because of disease presentation in terms of later stage or bulkier disease. The neoadjuvant space of course also provides an opportunity to assess treatment response and adapt the adjuvant treatment accordingly. So starting with the neoadjuvant space, I think using the classical taxane with dual antibody therapy, Herceptin, pertuzumab. I often use an anthracycline-based regimen, followed by taxane, Herceptin, pertuzumab to maximize volume reduction in the neoadjuvant space. Then moving into the adjuvant space, we can look to the APHINITY trial, as well as more recently the KATHERINE trial. Typically I’ll either continue dual anti-HER2 therapy with Herceptin and pertuzumab, and certainly for patients who have residual disease, especially those with a significant amount of residual disease, let’s say including the axilla, I am very likely to use T-DM1 [trastuzumab emtansine] in that setting.
Moving into the metastatic setting, I will say that the not quite long-term follow-up, but the data thus far, although not completely mature, are very promising in terms of reduction in risk of recurrence and development of metastasis after use T-DM1 in the adjuvant setting. That being said, in the first-line setting, people do of course recur. In the first-line setting, I typically use the classical CLEOPATRA regimen with taxane, Herceptin, pertuzumab. Being a Memorial Sloan Kettering Cancer Center practitioner, I typically use paclitaxel on a weekly basis and essentially turn on and off the Taxol based on the response to therapy. This gives us these periods of maintenance treatment with Herceptin and pertuzumab, which allows for a partner drug like hormone therapy in the setting of hormone receptor-positive disease. I think in the second-line space and beyond is where we really start to see practice variation because, fortunately, we now have treatment strategies that are more diverse than they used to be. Certainly we have in the second-line space T-DM1 that’s available to us and is listed in the NCCN [National Comprehensive Cancer Network] compendium. We have now tucatinib with capecitabine and Herceptin available for us in the second-line space. I think of this for my patients with brain metastases but also note the active systemic benefit of this combination.
Moving into the third-line space, we still have tucatinib, capecitabine, and trastuzumab available to us. We have trastuzumab deruxtecan available to us, the antibody-drug conjugate. We also have of course standard chemotherapy in combination with HER2 antibodies, and then of course moving on we have various combinations of chemotherapy with a TKI [tyrosine kinase inhibitor] like lapatinib. I did fail to mention neratinib. Neratinib is an option for us in combination with capecitabine in the third-line space and beyond. Finally, an agent that I don’t have much experience with because I am waiting for the data to mature is margetuximab, the engineered version of trastuzumab so to speak, in combination with chemotherapy. That’s technically available to us in the second-line space or beyond, but I don’t have much experience with margetuximab. My preferred option in the second-line space is T-DM1 or tucatinib with capecitabine and Herceptin. I’ll stop there. That was a bit of mouthful, but I hope that was the general overview you were looking for, V.K.
Vijayakrishna Gadi, MD, PhD: That was amazing, Dr Iyengar. Thank you so much.
Transcript edited for clarity.