Managing Sacituzumab AEs and Looking Forward to Next-Line TNBC Therapy

Hope S. Rugo, MD (Moderator)

Professor of Medicine

Director, Breast Oncology and Clinical Trials Education

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, CA

DISCUSSION QUESTION

• How do you counsel your patients with metastatic triple-negative breast cancer (TNBC) regarding sacituzumab govitecan-hziy (Trodelvy) with respect to toxicity?

HOPE S. RUGO, MD: Do you give patients information about the neutropenia and diarrhea risk before you start them?

CHRISTOPHER CHEN, MD: Yes, and also alopecia. Out of all the adverse events [AEs], the one that bothers my patient the most is her hair loss because she thought it was over and done with it already [after chemotherapy]. I started sacituzumab, and I warned her about the hair thinning, and that was probably the most intolerable AE for her.

RUGO: Do you have any patients using scalp cooling?

CHEN: No. I think it’s out of budget for a lot of my patients.

RUGO: There’s a philanthropic organization called HairToStay. We just did our fundraiser, and a lot of the haircare industry donates to it, as well as wealthy people, philanthropists, and some organizations donate to it. So, for example, some organizations that support a certain segment of the population will create their own funds, but they’ve given out tons of grants. I tell my patients to go to hairtostay.org because they can help with the costs. The patient still has some cost, but insurers will cover it now because there’s a Medicare code, so it’s worthwhile.

Dana-Farber Cancer Institute is doing a study [NCT04986579] looking at different scalp cooling techniques with sacituzumab. I’ve had quite a number of patients use it with good effect. Not everybody, but quite a number of patients do keep their hair. So it’s worth mentioning it to patients. It’s hard because they would be getting it day 1 and day 8 every 21 days and they have metastatic disease. They may not want to do it, but if hair is incredibly important to them, it is worth talking to HairToStay.

CHEN: I think it’s $1800; that is what our patients are telling me. That’s pretty pricey.

Rugo: Yes, it is. HairToStay will cover—I think their grants are $1500 and they have a sliding scale. But, if your patients can’t afford the $1800, it’s likely that they will qualify for the HairToStay grant. It’s worthwhile talking to them. They’re incredibly helpful. So, if a patient who is worried about losing their hair, then it’s worthwhile mentioning that. It depends on their insurance. I don’t think the California Medical Assistance Program or Medicaid would pay for it, but there are private insurers that have paid for the patient out-of-pocket cost, or at least a part of the cost, 80%. I think the Medicare code has a cap on the amount which is in the $1200 to $1500 range.

DISCUSSION QUESTION

• If you aren’t using sacituzumab govitecan in the second line, what are you using and why?
• What are you using most often as next-line therapy for progression on/after sacituzumab govitecan? ​

RITA MAITY MUKHERJEE, MD: I generally use sacituzumab, but if not, then eribulin [Halaven] is an alternative. If the patient is elderly or has more frailties, that is something I would use.

RUGO: What would you use next [after sacituzumab]?

MUKHERJEE: Eribulin.

RUGO: Do you start at a dose reduction for eribulin?

MUKHERJEE: I do. I’ve had some bad episodes, so I do generally use it and then go up.

RUGO: Growth factors are [used] almost always for patients on eribulin, andyou also get hair loss.

Does anybody else have a different drug they give in the next line?

CHEN: You also have to look at the HER2 expression. If it’s HER2-low disease, you have another option.

RUGO: You would give trastuzumab deruxtecan [Enhertu; T-DXd].

CHEN: Right. If their disease is HER2 low, it’s pretty effective.

RUGO: Yes. Although, in DESTINY-Breast04 [NCT03734029], there were just 58 patients with TNBC and 18 in the control arm, but the results were quite impressive.¹ I think that is a good next-line option and you could even use it after eribulin. Generally you can get it approved too, even though its sequencing, which wasn’t studied in DESTINY-Breast04.

Would anybody start with trastuzumab deruxtecan rather than sacituzumab if this was HER2-low disease?

BRENDA ERNST, MD: Yes, in a patient that did have HER2-low activity, I would start with that prior to sacituzumab.

RUGO: Why is that?

ERNST: Based on the tolerance that I’ve seen in patients, as well as the activity.

RUGO: [Although for patients with TNBC] it was a secondary analysis.

ERNST: Right.

ELISA BOMGAARS, MD: My impression was [T-DXd could be a] better treatment if the patient had brain metastases. Since TNBC has a higher risk for brain metastases, I thought that would hopefully help prevent it.

RUGO: I don’t know [if that is true]. I think that there are some data in patients with brain metastases with both drugs, but in small numbers of patients. The data for trastuzumab deruxtecan for HER2-positive brain metastases, even though the datasets are tiny, are quite intriguing. Even for leptomeningeal disease, [the results are] nice. But in TNBC, we don’t have that data in terms of preventing brain metastases or even treating them. But I think it’s a quite fascinating question and it will be addressed in one of the trials, [DESTINY-Breast12; NCT04739761]. I tend to use sacituzumab first because it has large robust phase 3 data with a survival benefit, but certainly we’ve seen these data in DESTINY-Breast04.

_Reference

_{1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690}