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Trastuzumab deruxtecan improved PFS vs chemotherapy in HR-positive, HER2-low metastatic breast cancer after 1 or more lines of endocrine therapy.
Treatment with fam-trastuzumab deruxtecan-nxki (Enhertu) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with standard-of-care (SOC) chemotherapy in patients with metastatic hormone receptor (HR)–positive, HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]–) breast cancer after 1 or more lines of endocrine therapy, according to topline results from the phase 3 DESTINY-Breast06 trial (NCT04494425).1
Furthermore, a statistically significant and clinically meaningful improvement in PFS was observed in the overall trial population, which included patients with HER2-low and HER2-ultralow disease (IHC 0 with membrane staining; IHC >0 <1+). Although overall survival (OS) data were not mature, a trend favoring trastuzumab deruxtecan was observed in both the overall and HR-positive, HER2-low populations.
No new safety signals were reported, and the safety profile of the antibody-drug conjugate was consistent with findings from previous clinical trials.
Full data from DESTINY-Breast06 will be presented at an upcoming medical meeting and shared with global health authorities.
“DESTINY-Breast06 shows that [trastuzumab deruxtecan] could become a new SOC for patients with HER2-low and HER2-ultralow metastatic breast cancer following 1 or more lines of endocrine therapy,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a news release. “These data underscore the potential for treatment with [trastuzumab deruxtecan] across the spectrum of HR-positive breast cancer, further redefining the treatment of metastatic breast cancer.”
In August 2022, the FDA approved trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. This approval was based on data from the phase 3 DESTINY-Breast04 trial (NCT03734029).2
DESTINY-Breast06 was a global, randomized, open-label trial that enrolled patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining; IHC >0 <1+) advanced or metastatic breast cancer. No prior chemotherapy for advanced or metastatic disease was permitted. Patients were required to have disease progression within 6 months of the initiation of first-line therapy consisting of endocrine therapy in combination with a CDK4/6 inhibitor, or they need to have at least 2 prior lines of endocrine therapy in the metastatic setting.1
Investigators enrolled 866 patients with HER2-low (n = 713) or HER2-ultralow (n = 153) disease across sites in Asia, Europe, North America, and South America.
Patients were randomly assigned to receive trastuzumab deruxtecan or chemotherapy, which consisted of capecitabine (Xeloda), paclitaxel, or nab-paclitaxel (Abraxane).
PFS per blinded independent central review (BICR) in patients with HR-positive, HER2-low disease served as the trial’s primary end point. Secondary end points included OS in the HER2-low population; PFS per BICR and OS in the overall trial population; objective response rate; duration of response; time to first subsequent treatment or death; time to second subsequent treatment or death; and safety. Notably, analyses of the HER2-ultralow subgroup are not powered to demonstrate statistical significance.
“The topline results from DESTINY-Breast06 highlight the importance of continuing to challenge current treatment paradigms and established breast cancer classifications to evolve how we treat patients with HR-positive, HER2-expressing metastatic breast cancer,” Ken Takeshita, global head of R&D at Daiichi Sankyo, added in a news release. “Building on the practice-changing data seen in DESTINY-Breast04, these results reinforce the potential for use of [trastuzumab deruxtecan] earlier in the treatment landscape and in an even broader patient population.”