FDA Grants Breakthrough Therapy Designation to DS-8201a and T-DXd to Treat Metastatic Breast Cancer

The FDA has granted fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo, AstraZeneca) breakthrough therapy designation for the treatment of unresectable or metastatic hormone receptor positive HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC >0 <1+) breast cancer. The treatment would be indicated for individuals that have received either 2 lines of endocrine therapy in the metastatic setting or 1 line of endocrine therapy that demonstrated disease progression within 6 months of starting first-line treatment with endocrine therapy, linked with a CDK4/6 inhibitor, or within 24 months of the start of adjuvant endocrine therapy, according to study authors.¹

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This marks the fourth breakthrough therapy designation for fam-trastuzumab deruxtecan-nxki in the metastatic breast cancer setting, according to study authors.¹

The study authors noted that, as of 2022, more than 2 million individuals were diagnosed with breast cancer with more than 665,000 deaths globally, making it the second most common cancer and leading cause of cancer death worldwide. Metastatic breast cancer occurs when the cancer has spread throughout the body as cancer cells break away from the original tumor. Approximately 30% of women that are diagnosed with early-stage breast cancer can develop metastatic breast cancer, which only has a 5-year survival rate.^1,2

Additionally, HER2 represents 15 to 20% of all breast cancer cases as a tyrosine kinase receptor growth-promoting protein that can be classified as positive or negative depending on the level of HER2 expression. The study authors noted that about 60 to 65% of HR positive, HER2 negative breast cancers are HER2 low.¹

Endocrine therapies are used as an early line of treatment for HR positive metastatic breast cancer. However, treatment is limited following 2 lines of endocrine therapy, and current standard forms of care relate to poor response rates. The study authors noted that fam-trastuzumab deruxtecan-nxki could offer an additional form of treatment as a HER2 monoclonal antibody that attaches to numerous topoisomerase I inhibitor payloads.¹

The breakthrough therapy designation was granted based on results from the randomized, open-label, phase 3 DESTINY-Breast06 trial that assessed the efficacy and safety of fam-trastuzumab deruxtecan-nxki 5.4 mg compared with capecitabine, paclitaxel, or nab paclitaxel chemotherapy among individuals with HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow advanced or metastatic breast cancer. The study included 866 individuals from Asia, Europe, North America, Oceania and South America that were not treated with chemotherapy to treat metastatic breast cancer and received endocrine therapy.¹

The study authors noted that the primary end point of the phase 3 study was progression-free survival (PFS) in the HR positive and HER2 low patient population, measured by blinded independent central review. The key secondary end points include PFS among the total trial population and overall survival among patients with low HER2.¹

“If approved, Enhertu could once again change the treatment paradigm for certain patients with breast cancer, pushing past old boundaries and broadening the number of people who may be eligible for a HER2 directed therapy,” Ken Takeshita, MD, global head of R&D at Daiichi Sankyo, said in a news release. “The designation also showcases Daiichi Sankyo’s commitment to pioneering cutting-edge science to deliver medicines like Enhertu that create new standards of care for patients with cancer.”¹

REFERENCES

1. Enhertu Granted Breakthrough Therapy Designation in U.S. for Certain Patients with HER2 Low or HER2 Ultralow Metastatic Breast Cancer. Business Wire. News release. August 19, 2024. Accessed August 19, 2024. https://www.businesswire.com/news/home/20240818195338/en/ENHERTU%C2%AE-Granted-Breakthrough-Therapy-Designation-in-U.S.-for-Certain-Patients-with-HER2-Low-or-HER2-Ultralow-Metastatic-Breast-Cancer.

2. Metastatic Breast Cancer. BreastCancer.org. News release. March 9, 2024. Accessed August 19, 2024. https://www.breastcancer.org/types/metastatic.