Early Stage HER2+ Breast Cancer: Optimizing Use of T-DM1


A brief discussion on the role of trastuzumab emtansine, T-DM1, in patients with early-stage HER2+ breast cancer.


Andrew Seidman, MD: I’d like to switch gears a little and talk about what to do after neoadjuvant therapy, when patients still have residual disease and when they don’t have residual disease. Bill, maybe you can take us back to KATHERINE and give us some guidance there.

William Gradishar, MD: In the past, the dilemma had been that if you had somebody who had residual disease, you weren’t guided by good data. We recognized at that time that patients like that had an increased risk of recurrence, but we didn’t have any data that suggested that by doing something—at that point, having received what we view as conventional therapy and perhaps completing the full year of trastuzumab—that you would confer an additional benefit on the patient. The KATHERINE study addressed that issue and demonstrated that in those with residual disease following preoperative therapy, T-DM1 [trastuzumab emtansine] reduced the risk of recurrence. It was a meaningful and clinically meaningful outcome. Based on that data, most oncologists—I’m sure including everyone here—adopted that as a strategy that should be employed for anybody who has residual disease.

Andrew Seidman, MD: There was a recent update that Terry Mamounas [MD] published in 2021 in Annals of Oncology showing the durability of that effect. There was no significant difference in central nervous system as a first site. I’d like to ask anyone on the panel what their experiences are in the ability to deliver the intended number of doses of T-DM1 [trastuzumab emtansine] in an adjuvant setting. Are there patients where you have to dose reduce, where you don’t get in all intended doses? VK, have you?

Vijayakrishna Gadi, MD, PhD: Yes, I had experience with this. We were at a site that participated in the ATEMPT trial. To refresh everybody’s memory, in that trial, patients with small tumors had the option of being randomized to the conventional approach at the time, which was paclitaxel-trastuzumab for a full year vs T-DM1 [trastuzumab emtansine]. The study is complicated. It had a different end point from just typical survival-type end points. But 1 thing we learned in that trial was that it was hard to give a full year of T-DM1 [trastuzumab emtansine]. A lot of patients started having neuropathies, platelet issues—a variety of complications. In the trial we’d stop and then bridge over to trastuzumab and get them to the full year. At the end of the day, in that trial, the patients who started T-DM1 [trastuzumab emtansine] numerically had better disease-free survival and other measures. It gives us some interest that we can get rid of the chemotherapy in the adjuvant setting by leaning on T-DM1 [trastuzumab emtansine], even for a full year. There’s now another study, ATEMPT 2.0, looking at that as a formal strategy to see if we can offload some of the toxicities. It may just be that a couple of months of T-DM1 [trastuzumab emtansine] is fine, and then you finish the day with trastuzumab.

Andrew Seidman, MD: Stephanie, in the KATHERINE setting, everyone has had taxane, so they’re possibly coming in with baseline neuropathy. Any thoughts about it?

Stephanie Graff, MD: Yes, that was included in the Mamounas follow-up. When they looked at the subgroup analysis they looked at data to see the recovery of the peripheral neuropathy that people entered the KATHERINE trial with. The rate of recovery of peripheral neuropathy was lower for patients that were getting T-DM1 [trastuzumab emtansine]. In my clinical practice, I’ve seen that in patients on T-DM1 [trastuzumab emtansine]. Periodically, but not often, I need to drop down to just trastuzumab as a single agent because the peripheral neuropathy is getting worse on T-DM1 [trastuzumab emtansine]. That’s OK because something is probably better than nothing in that population that had residual disease.

Andrew Seidman, MD: I always do try to go from 3.6 to 3.0 to 2.4 [mg/kg/dose] before jumping off the ship. Tiffany, in Asian patients in particular, we run into some more thrombocytopenia. Have you encountered this? Do you have any strategies or advice?

Tiffany Traina, MD: Yes, but just anecdotally. It’s been observed, but as oncologists, we’re pretty good at managing cytopenias and following guidance around dose modifications and reductions. Fortunately, we haven’t experienced complications like bleeding as a result of thrombocytopenia. As my colleagues have said, it requires a bit of management. Then we have the opportunity to switch to trastuzumab and pertuzumab again as needed.

Andrew Seidman, MD: I have a patient who was challenged by thrombocytopenia despite dose reduction, who very much believed in papaya extract as the solution. After 1 cycle of papaya extract, it looked as if she was having some benefit. We ended up using romiplostim to benefit, and we were able to continue her therapy.

Transcript edited for clarity.

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