Participants Consider the Necessity of Chemo in HER2+ Breast Cancer

Ian Krop, MD, PhD (Moderator)

Professor of Internal Medicine (Medical Oncology)

Yale School of Medicine

Director, Clinical Trials Office

Chief Clinical Research Officer

Associate Director, Clinical Sciences

Yale Cancer Center

New Haven, CT

IAN KROP, MD, PHD: For those of you who are selecting first-line regimens, what chemotherapy do you use? Do you use paclitaxel, or do you use docetaxel? Docetaxel is actually the one used in the in the original randomized trial.

SANTOSH KUMAR, MD: I usually use paclitaxel. I prefer using paclitaxel rather than docetaxel.

NAHEED ALAM, MD: I have used both. I have had good results with both.

KROP: They're both clearly effective. There are phase 2 studies using paclitaxel, and then there was the original phase 3 study using docetaxel. I think some oncologists, including myself, find that paclitaxel tends to be better tolerated in the metastatic setting, but it does require weekly visits, and docetaxel is typically given every 3 weeks so there is that issue. For some patients, frequency of visits can be an issue, and docetaxel helps that.

BARABRA CIVELLO, MD: The docetaxel regimen in some patients has a particular fatigue/asthenia component that is relevant and has to be considered.

KROP: I agree. Does anybody use other HER2 therapies besides trastuzumab [Herceptin] and pertuzumab [Perjeta]? Have you considered jumping to something like trastuzumab deruxtecan [Enhertu; T-DXd]?For those people who've done that, what were your reasons for starting with something other than trastuzumab/pertuzumab as your HER2 therapy?

INDER LAL, MD: [If] the time gap of the relapse is quite long, I think trastuzumab/pertuzumab makes sense to be re-tried. But if it was within 6 months, maybe then...you go to the second-line HER2 like T-DXd.

KROP: That is consistent with the way the trial was [done]. There was a trial looking at T-DXd in the second-line setting. But it did allow patients who had relapsed within 6 months of their adjuvant or neoadjuvant treatment. The guidelines now have been updated to say, even potentially if they've relapsed within 12 months, you can consider using what's typically considered a second-line therapy like T-DXd.

SUSANA M. CAMPOS, MD, MPH: How was that 6-month interval defined? I know clinically in gynecologic oncology that's been defined, although arbitrarily, that's probably not a good landmark. Also, when would you employ a tyrosine kinase inhibitor [TKI] targeting HER2/neu as maintenance, as opposed to continuing what you've discontinued?

KROP: In the trials and in practice, the way it's defined is the 6-month interval or 12-month interval, depending on the way you want to practice, is from the last dose of their adjuvant or neoadjuvant—in most cases, it's adjuvant—trastuzumab or trastuzumab/pertuzumab. So it's basically when they finish their antibody therapy that's when the clock starts—finish their adjuvant or HER2 therapy, not their endocrine therapy. I don't think it's very common, but some patients get adjuvant neratinib [Nerlynx] after their antibody therapy. You could count from when they finished their neratinib but that's pretty uncommon these days.

You also asked about TKIs. We generally don't use them in first-line therapy, but there are some situations where some people would use them in the second line.

Then in terms of maintenance therapy…in this patient case, she dropped the taxane and was on trastuzumab and pertuzumab as antibodies. Do you leave people on antibodies [only]? Or have you been using endocrine therapy for these patients? In the original trial, endocrine therapy wasn't allowed, but many of us knowing that there are some preclinical and clinical data suggesting that if you block the endocrine pathway with either aromatase inhibitor or other endocrine therapy, along with the antibodies, that you could potentially have better benefit. It hasn't been demonstrated in a definitive trial, but many of us do that, and I wondered if people thought about that in practice. This is after you've stopped the chemotherapy, and the patients is just on trastuzumab and pertuzumab, or even just on trastuzumab alone in your hormone receptor–positive patients. Do you tend to add an aromatase inhibitor or fulvestrant in that situation?

ALICIA M. DETRAGLIA, MD: [For a patient who has] triple-positive disease and went 3 years and didn’t have visceral disease, is there anybody who wouldn't give chemotherapy? Just give the anti-HER2 therapy and maybe the anti-endocrine therapy with a [CDK4/6 inhibitor], and not give the taxane to avoid the toxicity of that, since you're not curing her?

ALAM: In my experience, if the patient is presenting with a lot of bulk of disease, it is helpful in the beginning.

KROP: Yes, to try to reduce them, improve their symptoms, and then potentially switch to just antibodies or maintenance.

There was a substantially-sized trial that wasn't looking specifically at that question—it wasn't comparing chemotherapy vs a non-chemotherapy regimen—but it looked at endocrine therapy plus trastuzumab vs endocrine therapy plus trastuzumab and pertuzumab. It was called PERTAIN [NCT01491737], and it wasn't comparing against chemotherapy, but it allowed people to look at how patients did with only endocrine therapy and trastuzumab/pertuzumab. You could do inductive chemotherapy in that trial, which made it a little hard to interpret. But if you look specifically at the patients who didn't get chemotherapy, they had a median progression-free survival of approximately 27 months with endocrine therapy and trastuzumab/pertuzumab.¹ That's a select population, but I think to your point, it's an option that for select patients you could consider it in practice.

In practice, I don't think many of us see such patients very often, but you can imagine a patient with many comorbidities or very little disease burden who we can say could get benefit without having to use chemotherapy for a period of time. And for some patients, that probably is a worthwhile option.

REFERENCE:

Arpino G, de la Haba Rodríguez J, Ferrero JM, et al. Pertuzumab, Trastuzumab, and an Aromatase Inhibitor for HER2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer: PERTAIN Final Analysis. Clin Cancer Res. 2023;29(8):1468-1476. doi:10.1158/1078-0432.CCR-22-1092