Fam-trastuzumab deruxtecan-nxki (Enhertu), developed by Daiichi Sankyo and AstraZeneca, has received breakthrough therapy designation from the FDA for treating unresectable or metastatic hormone receptor-positive (HR+), HER2-low breast cancer. This designation applies to patients with IHC 1+, IHC 2+/ISH-, or HER2 ultralow (IHC >0 <1+) status who have progressed after two lines of endocrine therapy in the metastatic setting, or one line if disease progression occurred within six months of starting first-line endocrine therapy with a CDK4/6 inhibitor, or within 24 months of starting adjuvant endocrine therapy.
Mammogram image on a monitor – Image credit: okrasiuk | stock.adobe.com
This is the fourth breakthrough therapy designation granted to Enhertu for metastatic breast cancer. Breast cancer remains a significant global health concern, being the second most common cancer and a leading cause of cancer-related deaths. In 2022, over two million people were diagnosed with breast cancer, and more than 665,000 deaths were attributed to the disease worldwide. Metastatic breast cancer, which occurs when cancer spreads beyond the original tumor, develops in approximately 30% of women initially diagnosed with early-stage breast cancer, and carries a 5-year survival rate.
Microscopic image of breast cancer cells. – Image credit: Pharmacy Times
Understanding HER2 and Treatment Options
HER2, a tyrosine kinase receptor protein that promotes cell growth, is expressed in 15-20% of breast cancers. HER2 status (positive or negative) depends on the level of HER2 expression. About 60-65% of HR+, HER2-negative breast cancers are classified as HER2-low. Endocrine therapies are typically the first line of treatment for HR+ metastatic breast cancer. However, treatment options become limited after two lines of endocrine therapy, and current standard treatments often have poor response rates in these later stages. Fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody-drug conjugate carrying multiple topoisomerase I inhibitor payloads, offers a potential new treatment avenue.
The DESTINY-Breast06 Trial
The breakthrough therapy designation was based on findings from the DESTINY-Breast06 trial, a phase 3, randomized, open-label study comparing the efficacy and safety of fam-trastuzumab deruxtecan-nxki 5.4 mg/kg with capecitabine, paclitaxel, or nab-paclitaxel chemotherapy. The trial enrolled 866 patients with HR+, HER2-low advanced or metastatic breast cancer who had not received prior chemotherapy for metastatic disease but had received endocrine therapy. Participants were recruited from Asia, Europe, North America, Oceania, and South America. The primary endpoint was progression-free survival (PFS) in the HR+, HER2-low population, assessed by blinded independent central review. Key secondary endpoints include PFS in the overall trial population and overall survival in the HER2-low group.
Potential Impact on Breast Cancer Treatment
Dr. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, expressed optimism about the potential impact of Enhertu. He stated that if approved, Enhertu could reshape the treatment landscape for certain breast cancer patients, expanding the number of individuals eligible for HER2-targeted therapy. This designation underscores Daiichi Sankyo’s commitment to advancing scientific innovation and developing medicines that set new standards of care for cancer patients.
Conclusion
The breakthrough therapy designation for Enhertu offers a new hope for individuals with HR+, HER2-low metastatic breast cancer who have limited treatment options after progressing on endocrine therapy. The results of the DESTINY-Breast06 trial suggest that Enhertu may offer a significant improvement in progression-free survival. For personalized treatment plans and to discuss the latest advancements in breast cancer care, consult with a healthcare professional.
References
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.
Metastatic Breast Cancer. BreastCancer.org. News release. March 9, 2024. Accessed August 19, 2024. https://www.breastcancer.org/types/metastatic.
