Donahue Underscores Biggest Breast Cancer Treatment Changes for Nurses To Know in 2023

Sarah Donahue, MPH, AOCNP

Updated survival data from the DESTINY-Breast03 trial (NCT03529110)¹ and a landmark 4-year analysis of phase 3 monarchE (NCT03155997)² may represent readouts that have the largest effect on breast cancer practice heading into 2023, according to Sarah Donahue, MPH, AOCNP.

“One of the most exciting things was [data from] DESTINY-Breast03 showing that fam-trastuzumab deruxtecan-nxki [Enhertu] was better than ado-trastuzumab emtansine [Kadcyla]; T-DM1] in the second-line setting for metastatic HER2+ breast cancer patients [following] treatment with a taxane with pertuzumab [Perjeta]/trastuzumab [Herceptin],” said Donahue, a breast oncology nurse practitioner at the University of California, San Francisco, in an interview with Oncology Nursing News®.

“Often, after stopping treatment with a taxane, patients will continue with pertuzumab/trastuzumab for several months to years—or even indefinitely, in some wonderful cases,” she added. “[However], if these patients progress, [we’ve historically treated them with] T-DM1. They are now likely going to go on to receive trastuzumab deruxtecan, which is just so potent. I think that very exciting piece about it is that it is in increasing progression-free survival [PFS] and overall survival [OS] by so much. It is very, very effective.”

“Another thing that I thought was very interesting and hopeful was [the 4-year] abemaciclib [Verzenio] data for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer,” Donahue added. “We already know that abemaciclib improves invasive-disease-free survival. But now we know that even after patients stopped treatment, they continued to have benefit as long as 4 years. It’s really great to have those follow-up data.”

Donahue is the co-chair for the nursing track at the 40th Annual Miami Breast Cancer Conference® alongside Patricia Jakel, RN, MN, AOCN. Ahead of the conference, Donahue spoke with Oncology Nursing News® on the changes that she is most excited about integrating into clinical practice and what updates in the treatment landscape will be making it into her talk. Donahue discusses whether providers should push patients to receive germline testing for the BRCA gene or the ESR1 mutation in light of the approvals of 2022 approval of olaparib (Lynparza)³ and the 2023 approval of elacestrant (Orserdu),⁴ the challenges of assessing a patient’s risk profile, and the challenges she foresees with integrating certain therapies into the fold.

Oncology Nursing News®: As the landscape of clinically actionable mutations in breast cancer has expanded, how has your approach to determine who and what to test for change for patients with both early-stage disease and advanced disease?

Donahue: For patients with early-stage disease that is HER2-negatives, I’m more inclined to really press them to get germline testing done to see if they have a BRCA1 or BRCA2 mutation because adjuvant olaparib can really reduce their risk [of recurrence] by quite a bit.

Before if a patient had said, ‘Well, I don’t really want that,’ I would say ‘OK, I can’t make you get it, [but] I recommend you do it.’ Now I’d say ‘well, our treatment will be better for you if we really know the answer to this question.’

Over the past year, we found out that ESR1 mutations could indicate benefit from the new oral [selective estrogen receptor downregulator] SERD elacestrant. It is similar to our intermuscular SERD fulvestrant [Faslodex], but it was shown to have a benefit for patients with ESR1 mutations that have previously been treated with endocrine therapy along with the CDK4/6 inhibitors.

I’m really excited about [this therapy] and oral SERDs, mostly because it’s adding treatment options for our hormone receptor–positive patients, and we need more hormone-based therapies. [These agents are] generally easier to tolerate, [patients don’t need] to come in and get [intravenous] IV therapies. It is always wonderful to have something else to add, but what is even more exciting to me is the idea of having something as effective, [or] maybe even more effective than fulvestrant, that does not require intramuscular injection. Elacestrant is not going to replace fulvestrant, but it certainly gives us more options along that line of therapy.

What are some challenges for clinicians in determining patients who are at high risk of developing aggressive disease?

When a patient comes in, there are just so many factors that determine their risk. [The key is] putting it all together and creating a risk profile for them. Sometimes it’s obvious, but a lot of the times you’re in this gray zone where they have some quality about their cancer that is very high risk, and another quality that is low risk. What happens when you're collecting all sorts of data: you can get a muddled picture of things. It’s difficult to determine an individual’s risk level for that reason.

I love neoadjuvant chemotherapy; I find it to be so useful, but sometimes it can be quite confusing. I like the idea of giving patients endocrine therapy before surgery as their neoadjuvant therapy. It is really interesting for those patients who are hormone receptor–positive and HER2-negative when you’re trying to determine how sensitive their tumor is to the endocrine therapy and whether or not they’re going to have a good prognosis based on that and looking at things such as Ki-67 index—that can sort of make up for that confusing piece that happens when you have neoadjuvant chemotherapy in that hormone receptor–positive, HER2-negative population.

Also, with hormone receptor–negative [disease], there’s that challenge if you have a patient with a terrible-looking disease at baseline, and then you give them neoadjuvant therapy, and they have a wonderful response and achieve pathologic complete response. Now, in trying to think about what therapies to give them later—are you basing it on this pathologic complete response? Are you basing [your decision] on their baseline tumor? I don’t think we have enough data on what to do with patients with pathologic complete responses. Does that patient with a bilateral mastectomy or central node biopsy need to go on and get radiation because their tumor at baseline was so large? Is it just adding more toxicity to them and putting them at risk for lifelong lymphedema? So, I think that there’s so much more research to be done [in this arena].

What are some novel therapies that you’re looking forward to seeing integrated into practice? What challenges do they pose?

We’re going to have more people on sacituzumab govitecan-hziy [Trodelvy] now that it has been approved for patients that have hormone receptor–positive, HER2-negative metastatic disease,⁵ which are most of our patients. [Most practitioners] have experience with it in the triple-negative setting, so we’re just applying it to another group. I don’t think that these patients are that much different as far as how they would experience the drug and the adverse effects. [It’s possible] that hormone receptor–positive patients would have received many more prior lines of therapy before they receive sacituzumab govitecan so they may be at risk for more of the neutropenia that you see with it, but that is the only thing I could sort-of predict.

With trastuzumab deruxtecan—this medication is so effective, but it does have its own toxicities. [As providers, we need to] first, prevent the nausea and have patients get a lot of premedications and a lot of take-home meds to improve their experience. Also, having all the nurses be aware of the risk of [interstitial lung disease] ILD is key.

I’ll talk about ILD in my talk. It is a small risk, smaller than we initially thought, but it still is a very worrisome thing to have a patient experience. Being being able to recognize it and get patients on treatment quickly, or at least, to imaging quickly, is very important.

How has the approval of trastuzumab deruxtecan in the HER2-low setting changed approaches to sequencing?

Sequencing is changing in the HER2-positive population. We are going to be giving trastuzumab deruxtecan in the second line. I haven’t seen a patient that has progressed after their first line therapy since the DESTINY-Breast03 data came out, but it definitely would be the next choice. No doubt. I don’t think that there's a patient I wouldn’t give [trastuzumab deruxtecan] to you unless they had some horrible issue with their lungs where I felt nervous about that risk of ILD.

References

1. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023;401(10371):105-117. doi:10.1016/S0140-6736(22)02420-5
2. Johnstron SRD, Toi M, O’Shaughnessy JO; monarhE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77-90. doi:10.1016/S1470-2045(22)00694-5
3. FDA approves olaparib for adjuvant treatment of high-risk early breast cancer. March 11, 2022. FDA. Accessed February 20, 2023. bit.ly/3SG3yrl
4. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. FDA. Accessed February 20, 2023. bit.ly/3Hbxxln
5. FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. FDA. February 3, 2023. Accessed February 20, 2023. bit.ly/3IDjXZU