FDA Grants Priority Review to AstraZeneca’s Enhertu for HER2-Low or HER2-Ultralow Metastatic Breast Cancer

Image Credit: Adobe Stock Images/Axel Kock

The FDA has granted Priority Review to AstraZeneca’s Enhertu (trastuzumab deruxtecan) for treating patients with HER2-low or HER2-ultralow metastatic breast cancer who have received at least one line of endocrine therapy. According to the company, the Priority Review designation was based on promising data from the Phase III DESTINY-Breast06 trial, which demonstrated consistency in both HER2-low and HER2-ultralow subgroups.¹

“While endocrine therapies are widely used in the initial treatment of HR-positive metastatic breast cancer, most patients see limited benefit with additional lines of treatment, and subsequent chemotherapy is associated with poor response rates and outcomes. The results from DESTINY-Breast06 show that Enhertu 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,” said Susan Galbraith, EVP, oncology R&D, AstraZeneca, in a press release.

The global, randomized, open-label, DESTINY-Breast06 trial evaluated the efficacy and safety of Enhertu versus investigator’s choice of chemotherapy (capecitabine, paclitaxel, or nab-paclitaxel). Trial participants had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Investigators enrolled 866 patients across multiple sites in Asia, Europe, Australia, North America and South America.

The trial’s primary endpoint was progression-free survival in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Secondary endpoints include PFS by BICR in the overall trial population, overall survival (OS) in the HER2-low patient population and overall trial population, objective response rate, duration of response, time to first subsequent treatment or death, and time to second subsequent treatment or death, and safety.

Results indicated that Enhertu reduced the risk of disease progression or death by 37% compared to chemotherapy, with a median PFS of 13.2 months versus 8.1 months. In an analysis of patients with HER2-ultralow expression, Enhertu demonstrated a median PFS of 13.2 months versus 8.3 months with chemotherapy.¹

AstraZeneca warns that interstitial lung disease and fatal cases of pneumonitis can occur in patients treated with Enhertu. Comnon adverse events include nausea; decreased white blood cell count; decreased hemoglobin; decreased neutrophil count; decreased lymphocyte count; fatigue; decreased platelet count; increased aspartate aminotransferase; increased alanine aminotransferase; vomiting; increased blood alkaline phosphatase; alopecia; constipation; decreased appetite; decreased blood potassium; diarrhea, musculoskeletal pain; and abdominal pain.²

According to Susan G. Komen, it was estimated that in 2020, approximately 168,000 women in the United States were living with metastatic breast cancer. Six percent of women diagnosed with breast cancer in the United States are first diagnosed with metastatic breast cancer. Currently, around one-third of women diagnosed with metastatic breast cancer in the United States survive a minimum of five years after diagnosis, with some living 10 years or more.³

“This Priority Review highlights the potential to expand the existing indication of Enhertu 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. We look forward to working closely with the FDA with the goal of bringing Enhertu to more patients as quickly as possible,” said Ken Takeshita, global head, R&D, Daiichi Sankyo, in the press release.

Enhertu also recently received Breakthrough Therapy Designation in this indication, which is expected to accelerate its review by the FDA. The final decision is expected by early next year.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. AstraZeneca. October 1, 2024. Accessed October 1, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/enhertu-granted-priority-review-us-for-patients-her2-low-or-her2-ultralow-metastatic-breast-cancer-who-have-received-at-least-1-line-endocrine-therapy.html

2. IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNINGS. Enhertu. Accessed October 1, 2024. https://www.enhertuhcp.com/en/her2-low-breast/404

3. Metastatic Breast Cancer. Susan G. Komen. Accessed October 1, 2024. https://www.komen.org/breast-cancer/facts-statistics/what-is-breast-cancer/metastatic-breast-cancer/