Trastuzumab deruxtecan improves PFS in pretreated breast cancer
Click Here to Manage Email Alerts
CHICAGO — Trastuzumab deruxtecan extended PFS compared with standard chemotherapy for certain patients with pretreated breast cancer, according to findings presented at ASCO Annual Meeting.
The analysis — which included patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer that progressed after endocrine therapy — also showed considerably higher response rates with trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo).
“These results ... represent a potential shift in how we classify and treat metastatic breast cancer,” Giuseppe Curigliano, MD, PhD, of University of Milan and European Institute of Oncology, said in a press release. “We may have the opportunity to use trastuzumab deruxtecan earlier in the treatment of hormone receptor-positive metastatic breast cancer and expand trastuzumab deruxtecan [to patients with new metastatic breast cancer] who previously have not been able to benefit from a targeted medicine post-endocrine therapy.”
Approximately 60% to 75% of breast cancer cases are hormone receptor positive. About 50% are HER2 low, defined as an immunohistochemistry score for HER2 protein expression of 1+, or 2+ and in-situ hybridization negative. HER2-ultralow is defined as immunohistochemistry score greater than 0 but less than 1.
Background and methods
Chemotherapy is standard care for patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer who progressed after multiple lines of endocrine therapy with or without targeted therapy, or who progressed rapidly on prior adjuvant or first-line endocrine therapy.
However, the benefit of chemotherapy in this setting can be limited, highlighting the importance of identifying new treatment options that could delay progression and improve outcomes, according to study background.
Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate that consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads.
It is approved in the United States for several indications, including treatment of patients with HER2-low metastatic breast cancer whose disease progressed after chemotherapy.
The randomized phase 3 DESTINY-Breast06 trial assessed the efficacy and safety of the agent vs. investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) for 866 patients with hormone receptor-positive metastatic breast cancer.
All trial participants had received prior endocrine-based therapy and the majority (90.4%) had received targeted therapy with a cyclin dependent kinase 4/6 inhibitor. None had received chemotherapy for metastatic breast cancer.
The majority (82.3%; n = 713) had HER2-low disease, whereas 17.6% (n = 153) had HER2-ultralow disease.
Researchers randomly assigned 436 participants to 5.4 mg/kg trastuzumab deruxtecan every 3 weeks.
The other 430 received physician’s choice of chemotherapy (capecitabine, 59.8%; nab-paclitaxel, 24.4%; or paclitaxel, 15.8%).
PFS in the HER2-low population served as the primary endpoint. PFS in the intent-to-treat population (HER2-low and HER2-ultralow), OS, objective response rate and safety served as secondary endpoints.
Key findings
Researchers reported longer median PFS with trastuzumab deruxtecan in the HER2-low group (13.2 months vs. 8.1; HR = 0.62; 95% CI, 0.51-0.74) and the HER2-ultralow group (13.2 months vs. 8.3 months; HR = 0.78; 95% CI, 0.5-1.21).
ORR analyses favored trastuzumab deruxtecan in the HER2-low group (56.5% vs. 32.2%) and the HER2-ultralow group (61.8% vs. 26.3%).
Safety analyses showed serious side effects occurred among 41% of participants assigned trastuzumab deruxtecan and 31% of those assigned chemotherapy.
OS data remained immature at first interim analysis (HER2-low, HR = 0.83; 95% CI, 0.66-1.05; HER2-ultralow, HR = 0.75; 95% CI, 0.43-1.29).
Forty-nine patients (11.3%) assigned trastuzumab deruxtecan developed interstitial lung disease (ILD), and three died of ILD. One patient assigned chemotherapy developed ILD but survived.
A higher percentage of patients assigned trastuzumab deruxtecan experienced nausea (66% vs. 24%), fatigue (47% vs. 34%), alopecia (45% vs. 19%), neutropenia (38% vs. 28%), increased transaminases (29% vs. 11%), anemia (28% vs. 19%) and vomiting (27% vs. 9%).
Nausea was the most common adverse event that led to dose reductions (4.4%).
Grade 3 or higher drug-related adverse events occurred among 40.6% of patients assigned trastuzumab deruxtecan and 31.4% of those assigned chemotherapy.
Curigliano and colleagues will follow patients for OS, as well as to evaluate patient-reported outcomes.
They plan further research in hopes of identifying the threshold to determine which patients derive benefit from trastuzumab deruxtecan, Curigliano said during a press conference.
Collapse
Curigliano G, et al. Abstract LBA1000. Presented at: ASCO Annual Meeting; May 31-June 4, 2024; Chicago.
Click Here to Manage Email Alerts