Mridula George, MD, medical oncologist, Stacy Goldstein Breast Cancer Center, Rutgers Cancer Institute of New Jersey, assistant professor of medicine, Rutgers Robert Wood Johnson Medical School, discusses the evaluation of cardiotoxicity associated with adjuvant ado-trastuzumab emtansine (T-DM1; Kadcyla) with concurrent radiotherapy in patients with HER2-positive breast cancer.

Adjuvant T-DM1 is the current standard of care for patients with residual breast cancer after neoadjuvant HER2-targeted therapy. Additionally, patients at a high risk of recurrence are routinely offered adjuvant radiation.

Because T-DM1 is associated with a risk of cardiotoxicity, defined as a decline in left ventricular ejection fraction (LVEF), investigators conducted an institutional review of cardiotoxicity experienced by patients with stage I to III HER2-positive breast cancer treated with adjuvant T-DM1 and concurrent radiation, George says. During treatment, these patients were monitored by echocardiograms on intervals of at least 3 months to allow investigators to examine changes in cardiac function during treatment. Investigators collected data on age, date of diagnosis, history of cardiac disorders, echocardiogram findings, radiation dose, final pathologic stage, and molecular subtypes of cancer.

Findings presented at the 2022 San Antonio Breast Cancer Symposium showed that among 32 women examined during the review, 13 patients had left-sided breast cancer and received left-sided breast radiation. Additionally, 15 patients presented with a history of hypertension, putting them at increased risk for cardiac dysfunction, George notes.

LVEF was measured both pre- and post-treatment, and data showed that there was not a significant difference in LVEF in patients who received adjuvant T-DM1 and concurrent radiation, George explains.

However, 2 patients experienced a decline of more than 10% in LVEF. Notably, both patients were in their late 60s and had a history of hypertension, George explains. Treatment was discontinued in both patients, and both experienced a restoration of LVEF, George notes. No symptoms of heart failure were observed in these 2 patients, and they were both followed by cardiologists, George concludes.

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Mridula George, MD, discusses the evaluation of cardiotoxicity associated with adjuvant trastuzumab emtansine with concurrent radiotherapy in patients with HER2-positive breast cancer.

Dr. George on the Risk of Cardiotoxicity with Adjuvant T-DM1 Plus Radiotherapy in HER2+ Breast Cancer 

Mridula George, MD, medical oncologist, Stacy Goldstein Breast Cancer Center, Rutgers Cancer Institute of New Jersey, assistant professor of medicine, Rutgers Robert Wood Johnson Medical School, discusses the clinical implications of the phase 3 DESTINY-Breast04 trial (NCT03734029) in breast cancer. 

DESTINY-Breast04 evaluated fam-trastuzumab deruxtecan-nxki (Enhertu) vs physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer. Updated data from the trial were presented at the 2022 ASCO Annual meeting.

The DESTINY-Breast04 trial is one of the first positive studies in the HER2-low subgroup, George says. Prior clinical trials examining other HER2-targeted therapies have failed to generate a statistically significant benefit in efficacy for patients with HER2-low metastatic breast cancer, George says.

In DESTINY-Breast04’s first interim analysis, the key primary end points of progression-free survival (PFS) among patients with hormone receptor–positive, HER2-low breast cancer, and PFS in all enrolled patients, were met, George explains. Overall survival benefits were also observed, irrespective of HR status, George concludes.

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Mridula George, MD, discusses the clinical implications of the phase 3 DESTINY-Breast04 trial in breast cancer. 


Dr. George on the Importance of the DESTINY-Breast04 Trial in HER2-Low Breast Cancer

Mridula George, MD, medical oncologist, Stacy Goldstein Breast Cancer Center, Rutgers Cancer Institute of New Jersey, assistant professor of medicine, Rutgers Robert Wood Johnson Medical School, discusses the background of the phase 3 DESTINY-Breast04 trial (NCT03734029) in breast cancer.

DESTINY-Breast04 evaluated fam-trastuzumab deruxtecan-nxki (Enhertu) vs physician’s choice of chemotherapy in patients with HER2-low, hormone receptor (HR)–positive metastatic breast cancer. Updated data from the trial were presented at the 2022 ASCO Annual meeting.

Data from prior studies showed that trastuzumab deruxtecan elicited impressive response rates in heavily pretreated patients with HER2-low tumors, leading to further investigation of the antibody-drug conjugate in DESTINY-Breast04, George emphasizes.

The randomized, open-label, global trial enrolled about 500 patients, who were randomized 2:1 to receive trastuzumab deruxtecan or chemotherapy, George adds. Patients with HR-positive breast cancer should have progressed on prior hormonal therapy and between 1 or 2 lines of prior chemotherapy in the metastatic setting, George explains.

Patients with HR-negative, HER2-low breast cancer needed to progress on 1 or 2 prior lines of chemotherapy, George says. Notably, patients with interstitial lung disease or active brain metastases were excluded from the trial, George concludes.

Mridula George, MD, discusses the background of the phase 3 DESTINY-Breast04 trial in breast cancer.


Dr. George on the Background of the DESTINY-Breast04 Trial in HER2-Low Breast Cancer

Mridula George, MD, medical oncologist, Stacy Goldstein Breast Cancer Center, Rutgers Cancer Institute of New Jersey, assistant professor of medicine, Rutgers Robert Wood Johnson Medical School, discusses efforts to address unmet needs in HER2-low breast cancer.

The phase 3 DESTINY-Breast04 trial (NCT03734029) investigated fam-trastuzumab deruxtecan-nxki (Enhertu) vs. physician’s choice of chemotherapy in patients with unresectable or metastatic HER2-low breast cancer. This study was pivotal because there is currently no treatment for this subgroup of patients, George says.

DESTINY-Breast04 met its primary end point of progression free survival, plus the secondary end point of overall survival in the subgroup of patients with hormone receptor–positive disease, George explains.

Future research could explore potential combinations with trastuzumab deruxtecan, such as CDK4/6 inhibitors, George continues. The HER2-low space will generate more clinical trials to better understand treatment options for this subtype of breast cancer, George concludes.

Mridula George, MD, discusses efforts to address unmet needs in HER2-low breast cancer.


Mridula George, MD

Articles

Dr. George on the Risk of Cardiotoxicity with Adjuvant T-DM1 Plus Radiotherapy in HER2+ Breast Cancer

Dr. George on the Importance of the DESTINY-Breast04 Trial in HER2-Low Breast Cancer

Dr. George on the Background of the DESTINY-Breast04 Trial in HER2-Low Breast Cancer

Dr. George on Efforts to Address Unmet Needs in HER2-Low Breast Cancer