Dr. Gatti-Mays on Treating Patients With Endocrine-Resistant Breast Cancer

Advancements in Oncology, which took place on June 1, the second day of the 2024 American Society of Clinical Oncology Annual Meeting, brought together a panel of experts in breast, gastrointestinal, genitourinary, and lung cancers.

Co-hosts Rohit Gosain, MD, and Rahul Gosain, MD, MBA, known as The Oncology Brothers, spoke with breast cancer thought-leader Margaret Gatti-Mays, MD, MPH, of the Ohio State University Comprehensive Cancer Center.

Dr. Gatti-Mays—who also discussed hormone receptor (HR)-positive breast cancer and patients with HR-positive disease in the metastatic setting during her panel—moved along in the patient journey to endocrine-resistant disease.

“We’ve always thought about this binary idea when it comes to HER2 testing. It’s positive or negative. DESTINY-Breast04 changed that for us by saying, ‘Well, we have something here, [trastuzumab deruxtecan] (T-DXd)]. Now, you have to start labeling this as low HER2,’” Dr. Rahul Gosain said. Then he asked, “How important is testing HER2 when we’re talking about ultra-low [disease]? How sensitive are these tests?”

“HER2 testing is extremely important,” said Dr. Gatti-Mays. “I’ve always been very cautious, though…. It seems obvious from a pathologist’s perspective. It’s very clear if they’re 3+, less clear maybe if they’re 2+. But the difference between 1 and 0 is very small, and there’s not great inter-rater reliability based upon that differentiation.”

Dr. Gatti-Mays noted that she often asks pathologists for further analysis. “Especially if somebody is 0, I’ll say, ‘Can you take another look? Just find anything HER2.’ I think we do see benefit with Enhertu… For the patients who become endocrine resistant, Enhertu is definitely a reasonable option.” However, Dr. Gatti-Mays said it’s not necessarily the option she uses in all her patients because of the associated toxicities and side effects. “Capecitabine is still a great drug, so I try to work that in,” she said. “For tumors that involve the CNS, [capecitabine] is definitely favored, and I think some patients do tolerate it very well.”

After Dr. Rahul Gosain agreed with these sentiments, Dr. Gatti-Mays added that community oncologists should be aware that “patients can develop [interstitial lung disease] on [Enhertu].” She also noted that “it can be subtle. It’s not necessarily that patients are coming in and they’re on oxygen. I’ve had some patients who are completely asymptomatic, and we check in on staging scans. Sometimes it’s just a nagging cough, and with spring allergies and COVID, it can be very difficult to detect.” She cautioned that when using Enhertu earlier on, the risk-benefit ratio needs to be considered.

The discussion then shifted to next-generation sequencing, which Dr. Rohit Gosain called “critical in any form of malignancy today. Especially talking about T-DXd with pneumonitis,” he said. “We should not ignore the mildest form, especially when, as community oncologists, we’ll be utilizing it more and more.”

Dr. Rahul Gosain closed this portion of the panel discussion by asking Dr. Gatti-Mays: “You’ve used T-DXd, if that’s right for the patient. [Do you administer sacituzumab] or chemo?”

“I tend to use [sacituzumab] before I get to chemo,” said Dr. Gatti-Mays. “This developing area of data is showing that the second [antibody-drug conjugate (ADC)] probably does not work as well as the first ADC. There were quite a few posters at the annual meeting that showed that, and it’s consistent with what was presented previously. With the first ADC, we tend to get a robust response. With the second one, it’s maybe 50%.”

Dr. Rohit Gosain agreed with her insight, and then Dr. Gatti-Mays closed by saying, “Even though that second ADC may not work as well as the first, it’s still probably better than many of the chemotherapies. In many of my patients who do Enhertu, I’ll talk about or recommend sacituzumab. I think the other question that we as oncologists need to investigate is if we know sequential ADCs don’t work as well, is it worth maybe doing a chemotherapy and then coming back to ADCs? I think that question becomes more pertinent as we get more ADCs on our approval list.”