HER2-low metastatic breast cancer patients report preserved quality of life with trastuzumab deruxtecan treatment

MD Anderson presents patient-reported outcomes from DESTINY-Breast04 study



Patients who received trastuzumab deruxtecan (T-DXd) for human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer reported that the treatment maintained their quality of life (QoL) compared to conventional chemotherapy, according to results presented today by researchers from The University of Texas MD Anderson Cancer Center at the European Society for Medical Oncology (ESMO) Congress 2022.

Based on pre-defined patient reported outcome measures, researchers found that the time to definitive deterioration (TDD) for global health status/QoL with T-DXd was 11.4 months, compared to just 7.5 months with a physician’s choice of chemotherapy, signifying that T-DXd treatment delays the decline of QoL in patients with metastatic breast cancer.

“The DESTINY-Breast04 study reported improved progression-free survival and response rates and was practice-changing for patients with HER2-low metastatic breast cancer,” said presenting author Naoto Ueno, M.D., Ph.D., professor of Breast Medical Oncology. “We know the treatment was effective, but we wanted to hear from patients themselves to better understand how patients tolerated the treatment and how it impacted their overall health.”

The DESTINY-Breast04 study results previously published in the New England Journal of Medicine showed T-DXd, a HER2-targeting antibody-drug conjugate, doubled progression-free survival with compared to standard-of-care treatment with chemotherapy. It also significantly improved overall survival for patients with the HER2-low breast cancer subtype, which is a newly defined subset of HER2-negative breast cancer. In August 2022, the FDA approved T-DXd as the first targeted therapy for patients with HER2-low metastatic breast cancer.

The study treated 557 patients with advanced, unresectable and/or metastatic HER2-low breast cancer that were previously treated with one or two lines of chemotherapy. Patients enrolled in DESTINY-Breast04 were asked to complete questionnaires about their health-related QoL before, during and after treatment. Nearly all patients completed the three validated questionnaires at the start of the study, and at least 80% completed them at the specified time points for treatment cycles 2 to 27.

TDD, which is a measure of clinically meaningful deterioration, was defined as a stable change of 10 points or more relative to the beginning of the study for all patient-reported outcome measures. TDD was measured across the three PRO measures used in the study. The EuroQol 5-dimension questionnaire measures patients’ perception of their overall health using a numeric scale.

Global health status and QoL were measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 questionnaire (QLQ-C30). The questionnaire asks patients to rate, on a numeric scale, how they feel about their overall health and QoL, and how much difficulty they experienced in the last week with their symptoms or in carrying out specific everyday tasks.

The pain symptom scale showed a time to definitive deterioration of 16.4 months for patients who received T-DXd compared to only 6.1 months in those who received chemotherapy, which is important since pain is known to have a profound impact on patients' QoL.

For patients who were treated with T-DXd, global health status/QoL was maintained over the course of treatment, suggesting that treatment did not decrease patients’ reported health-related QoL.

“Most breast cancer patients who receive chemotherapy treatment have to reduce the number of cycles or discontinue therapy because of the side effects impacting their quality of life,” Ueno said. “It is encouraging that patients on the study saw a survival advantage and described no additional decline in quality of life. This data provides additional support for the potential benefits of T-DXd for patients with HER2-low metastatic breast cancer.”

Several ongoing studies are investigating the minimum HER2-expression threshold needed for T-DXd activity.

The study was funded by Daiichi Sankyo and AstraZeneca. Ueno has received institutional research grants and consulting fees from Daiichi Sankyo. A full list of co-authors and disclosures can be found here