T-DXd Earns FDA Priority Review in Pretreated HER2-Low Breast Cancer

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Data from DESTINY-Breast06 support the priority review designation for T-DXd as a treatment for HER2-low or HER2-ultralow breast cancer.

The FDA has set a Prescription Drug User Fee Act date for the first quarter of 2025 to approve T-DXd in this patient population.

The FDA has set a Prescription Drug User Fee Act date for the first quarter of 2025 to approve T-DXd in this patient population.

The FDA has granted priority review to trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for adults with unresectable or metastatic HER2-low or HER2-ultralow breast cancer previously treated with at least 1 type of endocrine therapy in the metastatic setting, according to a press release from the developers, AstraZeneca and Daiichi Sankyo.1

The FDA has set a Prescription Drug User Fee Act date for the first quarter of 2025 to approve T-DXd in this patient population.

“This priority review highlights the potential to expand the existing indication of [T-DXd] in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow,” Ken Takeshita, global head of Research and Development at Daiichi Sankyo, said in the press release.1 “We look forward to working closely with the FDA with the goal of bringing [T-DXd] to more patients as quickly as possible.”

Supporting findings for the priority review designation came from the phase 3 DESTINY-Breast06 trial (NCT04494425) evaluating treatment with T-DXd vs investigator’s choice of chemotherapy among patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow advanced or metastatic breast cancer. Investigators presented updated findings from DESTINY-Breast06 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.2

Data showed a median progression-free survival (PFS) of 13.2 months with T-DXd compared with 8.1 months using chemotherapy among patients with HER2-low disease (HR, 0.62; 95% CI, 0.51-0.74; P <.0001). Across the intent-to-treat (ITT) population, the median PFS was 13.2 months vs 8.1 months in each respective arm (HR, 0.63; 95% CI, 0.53-0.75; P <.0001). For those with HER2-ultralow disease, data showed a median PFS of 13.2 months vs 8.3 months in each arm (HR, 0.78; 95% CI, 0.50-1.21).

In the T-DXd and chemotherapy arms, respectively, the confirmed objective response rate (ORR) was 56.5% vs 32.2% among patients with HER2-low disease, 57.3% vs 31.2% in the ITT population, and 61.8% vs 26.3% in the HER2-ultralow subgroup.

Overall, 98.8% and 95.2% of patients in the T-DXd and chemotherapy arms, respectively, had any-grade treatment-emergent adverse effects (TEAEs). The most common any-grade drug-related TEAEs in each arm included nausea (65.9% vs 23.5%), fatigue (46.8% vs 34.3%), and alopecia (45.4% vs 19.4%).

“Including HER2-ultralow [disease], the proportion of patients who could benefit from T-DXd will be close to 85% in hormone receptor–positive, HER2-negative breast cancer,” lead study author Giuseppe Curigliano, MD, PhD, a professor of Medical Oncology at the University of Milan and the Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy, said in a presentation of these data at ASCO.

In the multi-center, open-label DESTINY-Breast06 trial, patients with HER2-low or HER2-ultralow metastatic breast cancer were randomly assigned 1:1 to receive T-DXd at 5.4 mg/kg every 3 weeks (n = 436) or investigator’s choice of chemotherapy (n = 430). Treatment in the comparator arm consisted of capecitabine (Xeloda), nab-paclitaxel, or paclitaxel.

The trial’s primary end point was PFS in the HER2-low population. Secondary end points included PFS in the ITT population and overall survival in the HER2-low and ITT populations.

The FDA previously granted breakthrough therapy designation to T-DXd for unresectable or metastatic HR-positive, HER2-low, or HER2-ultralow breast cancer in August 2024 based on findings from DESTINY-Breast06.3

“The results from DESTINY-Breast06 show that [T-DXd] has the potential to evolve the current HR-positive treatment landscape and become the first targeted treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, concluded.1

References

  1. Enhertu granted Priority Review in the US for patients with HER2-low or HER2-ultralow metastatic breast cancer who have received at least one line of endocrine therapy. News release. AstraZeneca. October 1, 2024. Accessed October 1, 2024. https://tinyurl.com/bdh6vdad
  2. Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): primary results from DESTINY-Breast06 (DB-06). J Clin Oncol. 2024;42(suppl 17):LBA1000. doi:10.1200/JCO.2024.42.17_suppl.LBA1000
  3. ENHERTU® granted breakthrough therapy designation in U.S. for certain patients with HER2 low or HER2 ultralow metastatic breast cancer. News release. Daiichi Sankyo. August 19, 2024. Accessed October 1, 2024. https://tinyurl.com/2k9bfnp2
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