Part 2: Managing Sacituzumab-Associated Neutropenia in TNBC

Sara Tolaney, MD, MPH

Chief of Breast Oncology and Associate Director

Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute

Associate Professor, Harvard Medical School

Targeted Oncology^TM: How can physicians manage the neutropenia associated with sacituzumab govitecan (Trodelvy)?

SARA TOLANEY, MD, MPH: Our group has done a lot of things. Some physicians use filgrastim [Neupogen], or granulocyte colony-stimulating factor [G-CSF], after day 1, for 3 or 4 days, and then use the on-body pegfilgrastim [Neulasta] on day 9. I’ve heard some physicians give prophylactic growth factor, which is not commonly done in our group. We usually wait for the neutropenia, and then I’ve given some patients only day 9 pegfilgrastim. You can also dose reduce and follow patients.

Interestingly, the ASCENT study [NCT02574455] did an analysis looking at patients who had dose modification, and looked at progression-free survival and overall survival in that population compared with patients without dose modification.^1,2 In fact, outcomes are the same. It showed that those patients were able to keep on schedule, and that’s probably why they did well. In the study, a little under half of all patients did require G-CSF, even on the ASCENT trial. I will say that neutropenia is probably the most common thing I deal with in clinic.

What did physicians in the ASCENT trial do to manage neutropenia and other adverse events?

That was per physician discretion, in terms of filgrastim or pegfilgrastim. Nausea prophylaxis is also recommended. I generally use dexamethasone with ondansetron [Zofran] or dexamethasone with palonosetron [Aloxi]; some physicians use aprepitant [Emend]. You do need to think about nausea prophylaxis with this drug because patients get nauseous. Prophylaxis is recommended with the infusion, and then I typically use pro re nata antiemetics and that seems to work well. For diarrhea, I think loperamide as needed is usually adequate for many patients.

Are there challenges getting insurance to approve drugs for mitigating neutropenia?

In some cases, I give the filgrastim on days 2, 3, and 4, and then I use the pegfilgrastim, where it’s dispensed in the infusion center. I have not had as much of a problem with that. But I’ve never been able to give 2 prescriptions for outpatient self-injection of pegfilgrastim and the G-CSF because insurance won’t let me do that. I have been denied from doing both, and that becomes [difficult]. I had to have a patient use G-CSF after day 1 and day 8, which is annoying to give themselves so many shots. This is something we’ve discussed with the [manufacturer] a lot because I think they need to come up with a better system for the growth factor, because it is so necessary with this agent. It’s [difficult] to deal with all the insurance approvals, that are needed for the vast majority of patients getting this drug.

What are the day 8 absolute neutrophil counts that make you use filgrastim?

Truthfully, I do it with anything under 1000 cells/uL, so [if patients have] 700 to 800 cells/uL…I have to delay [treatment] when they come in with [low neutrophil count]. But then moving forward, for all their subsequent cycles, since I know they didn’t do well with day 8, I’ve started giving them growth factor after each. I will say my biggest issue with sacituzumab is all the growth factor support. But, other than that, I find that people do well.

Do you check UGT1A1 status before giving the medication?

Truthfully, I haven’t been. But one could argue if I should be, because if you look at the data that were presented, where they looked at patients with the *28/*28 homozygous status, those patients did have high rates of neutropenia and more diarrhea.³ So, in the label it does not state that you have to check, but if you know a patient has homozygous *28/*28 status, then you should think about dose modification in those patients. So, I haven’t been checking, but again, one can argue that it’s not unreasonable to check. And, knowing what we know, toxicity is far greater in those patients, and that starting with dose modification those patients may be reasonable.

_References:

_{1. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485}

_{2. Spring LM, Nakajima E, Hutchinson J, Viscosi E, et al. Sacituzumab govitecan for metastatic triple-negative breast cancer: clinical overview and management of potential toxicities. The Oncol. 26: 827-834. doi:10.1002/onco.13878}

_{3. Bardia A, Messersmith WA, Kio EA, et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol. 2021;32(6):746-756. doi:10.1016/j.annonc.2021.03.005}