Fam-trastuzumab deruxtecan-nxki (T-DXd) delayed cancer growth in patients with hormone receptor (HR)-positive, HER2-low or -ultralow metastatic breast cancer that progressed following endocrine therapy, according to findings from the phase III DESTINY-Breast06 trial. The research was presented by Giuseppe Curigliano, MD, PhD, and colleagues at the 2024 ASCO Annual Meeting (Abstract LBA1000).
Giuseppe Curigliano, MD, PhD
About DESTINY-Breast06
This study included 866 patients with metastatic breast cancer that was either HER2-low (713 participants) or HER2-ultralow (153 participants). HER2-low cancers were classified as those with an immunohistochemistry score that indicates the amount of HER2 protein expressed in cancer cells of 1+ or 2+, while HER2-ultralow cancers had a score of greater than 0 but less than 1+. All study participants had received at least one prior endocrine therapy, and nearly all participants (90.4%) had also received targeted therapy with a CDK4/6 inhibitor. The participants were randomly assigned to receive either T-DXd (n = 436) or investigator’s choice of chemotherapy (n = 430, who received either capecitabine, nab-paclitaxel, or paclitaxel).
Key Findings
For those with HER2-low cancer, the median progression-free survival was 13.2 months for those who received T-DXd vs 8.1 months for those who received chemotherapy. Similar results were seen in the small group of patients with HER2-ultralow cancer. Overall, patients with HER2-low cancer who received T-DXd had a 38% lower chance of their cancer growing or spreading compared to those who received chemotherapy.
For those with HER2-low cancer, the objective response rate was 56.5% for those who received T-DXd vs 32.3% for those who received chemotherapy. For those with HER2-ultralow cancer, the objective response rate more than doubled in those who received T-DXd compared with those who received chemotherapy—61.8% vs 26.3%, respectively.
Patients who received T-DXd were able to receive treatment for a longer duration without experiencing severe side effects, with a median treatment length of 11 months vs 5.6 months for those who received chemotherapy. Serious side effects were more common in the T-DXd group, with about 41% of participants experiencing a serious side effect vs about 31% of those who received chemotherapy.
Interstitial lung disease (ILD), a known side effect of T-DXd, occurred in about 11% of participants receiving the drug, which is consistent with previous research. ILD was not serious for most participants; however, about 5% of the participants discontinued treatment due to ILD, and three died from this toxicity. The most common serious side effect that led to reducing the dose of T-DXd was nausea (occurring in 4.4% of participants).
“These results also represent a potential shift in how we classify and treat metastatic breast cancer, as we may have the opportunity to use [T-DXd] earlier in the treatment of HR-positive metastatic breast cancer and expand T-DXd into new metastatic breast cancer patients who previously have not been able to benefit from a targeted medicine post–endocrine therapy,” said lead author Dr. Curigliano, of the University of Milan and European Institute of Oncology.
Next Steps
The researchers are planning to continue following the patients to assess overall survival outcomes. They will also continue to analyze data from other secondary endpoints, including patient-reported outcomes, as well as undertake exploratory translational analyses.
ASCO Perspective
Erica L. Mayer, MD, MPH
“Antibody-drug conjugates are an exciting and effective part of breast cancer care with a growing role in our treatment paradigms. T-DXd, an antibody-drug conjugate approved for pretreated metastatic HER2-positive and HER2-low breast cancer, was evaluated in the DESTINY Breast06 trial as the first therapy for patients with HR-positive, HER2-low, and HER2-ultralow breast cancer after endocrine therapy. In comparison to standard chemotherapy, T-DXd significantly improved progression-free survival, with similar results in both HER2-low and HER2-ultralow disease,” said Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute.
“These data suggest that T-DXd may become a preferred first-line treatment option for most patients with HR-positive metastatic breast cancer after progression on endocrine therapy. It is important to note, however, that trastuzumab deruxtecan resulted in more serious toxicities compared to traditional chemotherapy, and may not be the right choice for every patient,” she commented.
Disclosure: The DESTINY-Breast06 study was funded by AstraZeneca and Daiichi Sankyo. For full disclosures of the study authors, visit coi.asco.org.
