Trastuzumab Deruxtecan Improves Outcomes for Patients with Progression After Endocrine Therapy
A study presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) demonstrated the efficacy of trastuzumab deruxtecan compared to chemotherapy in patients with breast cancer and disease progression after endocrine therapy, with particular benefit seen among patients with rapid disease progression.
In the phase 3 DESTINY-Breast06 clinical trial, researchers randomly assigned patients with metastatic breast cancer and disease progression after one or more endocrine therapy to trastuzumab deruxtecan or physician’s choice of chemotherapy. Results of the primary analysis showed a significant progression-free survival benefit with trastuzumab deruxtecan (median, 13.2 months vs 8.1 months).
At SABCS, researchers presented additional analyses based on subgroups. Patients had at least two prior lines of endocrine-based therapy for metastatic breast cancer, or one line if progressive disease occurred within 24 months of adjuvant therapy or within 6 months of first-line endocrine therapy with a CDK4/6 inhibitor. The latter was considered rapid progression.
The two groups had similar mean global health status scores at baseline (endocrine therapy vs radiation therapy, 75.5 ± 19.3 vs 71.9 ± 19.1). However, the mean change from baseline over the course of 24 months was higher among patients assigned to endocrine therapy (-10 ± 25.8 vs -1.1±18.8).
The analysis, based on time to progression, included 124 patients with disease progression within 6 months; 112 patients with disease progression within 6-12 months; and 334 patients with disease progression at 12 months or longer. Progression-free survival favored assignment to trastuzumab deruxtecan at all points of progression.
The confirmed objective response rates also favored trastuzumab deruxtecan for patients with rapid progression (67.7% vs 25.4%), as well as other time points (6-12 months, 60% vs 28.8%; ≥ 12 months, 59.5% vs 33.1%).
Median duration of response also favored trastuzumab deruxtecan in every subgroup (< 6 months, 11.1 months vs 7.3 months; 6-12 months, 13.7 months vs 11.5 months; ≥ 12 months, 15.7 months vs 11.1 months).
Similar efficacy outcomes were observed by the researchers for patients with primary and secondary endocrine resistance.
The incidence of grade 3 or higher adverse events for trastuzumab deruxtecan versus chemotherapy was similar for the intent-to-treat population in patients with rapid progression (55.4% vs 42.4%), as well as other subgroups (6-12 months, 59.3% vs 40.8%; ≥ 12 months, 45.8% vs 42.9%).
“Results highlight the potential role of trastuzumab deruxtecan as an early-line treatment after one or more lines of endocrine-based therapy for patients with HR-positive, HER2-low or -ultralow metastatic breast cancer.”
-Aditya Bardia, MD, MPH, professor of medicine and director of translational research integration, UCLA Jonsson Comprehensive Cancer Center
Disclosures: The DESTINY-Breast06 clinical trial is supported by AstraZeneca. See the full study for details.
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