3D rendered medically accurate illustration of a breast cancer: © SciePro - stock.adobe.com

A statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed among patients with hormone receptor (HR)-positive, HER2-low, metastatic breast cancer following 1 or more lines of endocrine therapy when treated with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) vs standard-of-care (SOC) chemotherapy, according to findings from the primary population of the phase 3 DESTINY-Breast06 trial (NCT04494425).¹

A similar PFS benefit was seen in the overall trial population of patients with HER2-low and HER2-ultralow metastatic breast cancer. The clinically meaningful improvement was consistent in a prespecified subgroup analysis between patients with HER2-low and HER2-ultralow expression.

While overall survival (OS) data were not mature at the time of this analysis, the trial is planned to continue and will further assess OS as well as other secondary end points. Data from this study are expected to be shared with global regulatory authorities and presented at an upcoming medical meeting.

“DESTINY-Breast06 shows that [T-DXd] could become a new standard of care for patients with HER2-low and HER2-ultralow metastatic breast cancer following 1 or more lines of endocrine therapy. These data underscore the potential for treatment with [T-DXd] across the spectrum of HR-positive breast cancer, further redefining the treatment of metastatic breast cancer,” said Susan Galbraith, executive vice president, oncology research and development, AstraZeneca, in a press release.

While the OS data were not mature, T-DXd demonstrated an early trend towards an OS improvement compared with SOC chemotherapy in the overall trial population, as well as in those with HER2-low metastatic breast cancer.

Looking at safety, treatment with T-DXd did not generate any new safety signals. The safety profile of the agent was also consistent with reports from previous breast cancer clinical trials.

“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. Building on the practice-changing data seen in DESTINY-Breast04 [NCT03734029], these results reinforce the potential for use of [T-DXd] earlier in the treatment landscape and in an even broader patient population,” said Ken Takeshita, global head, research and development, Daiichi Sankyo, in a press release.

About DESTINY-Breast06

The phase 3, global, randomized, open-label DESTINY-Breast06 trial is assessing the efficacy and safety of T-DXd at a dose of 5.4 mg/kg vs investigator’s choice of chemotherapy, consisting of capecitabine, paclitaxel or nab-paclitaxel, for the treatment of patients with HR-positive, HER2-low or HER2-ultralow, advanced or metastatic breast cancer.²

Enrollment in the study was open to patients aged 18 years and older who had received no prior chemotherapy for advanced or metastatic disease and had adequate tumor samples for assessment of HER2 status. Patients must have experienced disease progression within 6 months of starting first-line treatment with an endocrine therapy combined with a CDK4/6 inhibitor or received at least 2 prior lines of treatment with an endocrine therapy in the metastatic setting. Additionally, all patients were required to have adequate organ and bone marrow function.

Investigators are evaluating the primary end point of PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Secondary end points being explored in the trial include OS in patients with HER2-low expression, PFS by BICR in the overall trial population, 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.

A total of 866 patients were enrolled in the DESTINY-Breast06 trial, including 713 patients with HER2-low disease and 153 with HER2-ultralow disease. Patients were enrolled at multiple sites in Asia, Europe, North America, and South America.¹

REFERENCES:

1. Enhertu demonstrated statistically significant and clinically meaningful improvement in progression-free survival in HR-positive, HER2-low metastatic breast cancer following one or more lines of endocrine therapy in DESTINY-Breast06 phase III trial. News release. AstraZeneca. April 29, 2024. Accessed April 29, 2024. https://tinyurl.com/msusxxuc

2. Study of trastuzumab deruxtecan (T-DXd) vs investigator's choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer (DB-06). ClinicalTrials.gov. Updated April 12, 2024. Accessed April 29, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04494425