HER2-Positive Breast Cancer - Episode 9

Case 2: Recurrence of HER2+ Breast Cancer After 12 Months

Targeted Oncology

Carey Anders, MD, and Andrew Seidman, MD, share their recommendations for HER2+ breast cancer recurrence within 12 months of HP.

Sara Tolaney, MD, MPH: Let’s pretend this is the scenario. Let’s say someone got their HP [trastuzumab, pertuzumab] and was on their adjuvant AI [aromatase inhibitor] but recurred about 12 months after their last dose of adjuvant HP [trastuzumab, pertuzumab]. How would you think about that patient? Carey, what would you do as first-line therapy in that scenario? Would it be different from the THP [docetaxel, trastuzumab, pertuzumab] regimen, knowing the disease-free interval is shorter?

Carey Anders, MD: Within a year of completion of the HP [trastuzumab, pertuzumab], unfortunately that’s usually the scenario we’re in. I agree it’s more unusual to have a 5-year disease-free interval, but it does happen. Certainly not under a year, but after 12 months or greater, I will consider going back to trastuzumab-pertuzumab. Andy, I usually use weekly paclitaxel in that setting, in the metastatic setting. We’re in the marathon, not the sprint. But I would also be close on the line about going on to T-DM1 [trastuzumab emtansine] as the ADC [antibody-drug conjugate] in second line. It would also depend on the burden of disease. When I have a patient recur with ER [estrogen receptor]–negative, HER2 [human epidermal growth factor receptor 2]–positive breast cancer, I tend to use the CLEOPATRA regimen if it has been 12-plus months. But in the ER+ space, in the setting of particularly bone only, which we’ve seen many times will lead with endocrine therapy, trastuzumab-pertuzumab, and I haven’t yet incorporated any other biologic. I know the data for the MonarcHER are quite promising. The data have a lot of biologic rationale, but I haven’t done it off protocol. It’s interesting. Andy, you commented that resistance is not static; it can be dynamic. I do go back, and I also think about that comment of the marathon, of the sprint. What if I had 12 additional months of disease stability on trastuzumab, pertuzumab, and fulvestrant? From a toxicity perspective, that’s quite impressive. Then I’m able to move into second line. For anything under a year, I’m going to start moving to second-line therapy.

Sara Tolaney, MD, MPH: That’s probably the consensus at this group, probably, with that 12-month cutoff—a little arbitrary, in truth—for when we would switch to thinking about T-DM1 [trastuzumab emtansine]. Let’s pretend this patient did recur at that 60-month mark, went on to get THP [docetaxel, trastuzumab, pertuzumab] as many people tend to do, either treat to maximal response or onset of a little toxicity. Then we tend to drop the taxane. How are you guys approaching that patient on that maintenance HP [trastuzumab, pertuzumab] portion if they had ER+ disease? Do you add in endocrine therapy? Would you in someone who recurred on their AI? What endocrine agent would you choose? Andy?

Andrew Seidman, MD: I agree with Ingrid. This is not a common case. But if the case did present itself, upon stopping taxane and continuing HP [trastuzumab, pertuzumab], I’d first continue HP [trastuzumab, pertuzumab] as subcutaneous HP [trastuzumab, pertuzumab]. When she came in for her subcutaneous HP [trastuzumab, pertuzumab], she’d probably come in for fulvestrant as well. I would target both HER2 and ER and I wouldn’t swap 1 AI for another. I would go to a SERT [serotonin reuptake transporter].

Carey Anders, MD: I agree.

Sara Tolaney, MD, MPH: The only tricky thing is the timing in making the patients come in occasionally off kilter from one another. When I’ve got that fulvestrant HP [trastuzumab, pertuzumab], it’s a little annoying.

Sara Tolaney, MD, MPH: Certainly there are a lot of trials ongoing in this space and this maintenance phase that are trying to add on targeted agents. One trial is PATINA, which is looking at adding a CDK4/6 inhibitor, in this case, palbociclib, to that maintenance endocrine therapy, HP [trastuzumab, pertuzumab] setting. There are also studies looking at kinase inhibition in the PIK3CA-mutant patient in this maintenance setting. We’ll see more to come, and how to approach these ER+ patients when they’re in maintenance. Hopefully we’ll see further improvements.

Transcript edited for clarity.