European Commission Approves Trastuzumab Deruxtecan for HER2-Low Metastatic Breast Cancer

January 26, 2023

Fam-trastuzumab deruxtecan-nxki has received approval in the European Union as a single agent for the treatment of patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy for metastatic disease or developed disease recurrence during or within six months of completing adjuvant chemotherapy.

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) has received approval in the European Union as a single agent for the treatment of patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy for metastatic disease or developed disease recurrence during or within six months of completing adjuvant chemotherapy.¹

The approval was based on findings from the phase 3 DESTINY-Breast04 trial (NCT03734029), which demonstrated a 50% reduction in the risk of disease progression or death and a 36% reduction in the risk of death with T-DXd compared with physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer with hormone receptor–positive or –negative disease.

The median progression-free survival was 9.9 months (95% CI, 9.0-11.3) and 5.1 months (95% CI, 4.2-6.8) with T-DXd and chemotherapy, respectively (HR, 0.50; 95% CI, 0.40-0.63; P < .0001). The median overall survival was 23.4 months (95% CI, 20.0-24.8) and 16.8 months (95% CI, 14.5-20.0), respectively (HR, 0.64; 95% CI, 0.49-0.84; P = .001).

“The European approval of trastuzumab deruxtecan in the HER2-low metastatic breast cancer population marks the first time we will have the opportunity to treat patients with lower levels of HER2 expression with a HER2-directed therapy,” Javier Cortés, MD, PhD, head of the International Breast Cancer Center in Barcelona, Spain, said in a press release. “Trastuzumab deruxtecan has shown a significant improvement in outcomes compared to chemotherapy for these patients, reinforcing its potential to become a new standard of care.”

The regulatory decision follows a positive recommendation supporting the approval of T-DXd in this population from the European Medicines Agency’s Committee for Medicinal Products for Human Use.²

“The approval of trastuzumab deruxtecan in HER2-low metastatic breast cancer represents a significant clinical advance for patients in Europe with both hormone receptor–positive and hormone receptor–negative disease who previously have had limited treatment options in the late-line setting,” Ken Keller, global head of Oncology Business, and president and chief executive officer of Daiichi Sankyo, Inc, said. “This milestone also supports our vision to bring trastuzumab deruxtecan to more patients across the HER2 spectrum, which requires a change to the breast cancer classification system that has been guiding treatment for more than two decades.”

In DESTINY-Breast04, the safety profile of T-DXd mirrored past trial data with no new safety concerns identified. Grade 3 or grade 4 treatment-related adverse effects (AEs) from a pooled safety analysis of patients who received the 5.4 mg/kg dose of trastuzumab deruxtecan across tumor types included neutropenia (16.3%), anemia (9.2%), fatigue (7.5%), leukopenia (6.3%), thrombocytopenia (5.9%), nausea (5.6%), lymphopenia (4.8%), transaminases increased (3.9%), hypokalemia (3.5%), vomiting (2.2%), pneumonia (1.9%), diarrhea (1.8%), decreased appetite (1.7%), febrile neutropenia (1.2%), dyspnea (1.2%), blood bilirubin increased (1.1%), ejection fraction decreased (1.1%), and musculoskeletal pain (1.1%). Grade 5 AEs occurred in 1.5% of patients, including interstitial lung disease (1.2%).

“Historically, patients with breast cancer who have tumors with low levels of HER2 expression have been classified as HER2 negative, giving them limited treatment options beyond chemotherapy,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, added. “This approval reinforces the important role trastuzumab deruxtecan may have for patients with HER2-low disease and highlights the need to evolve the way breast cancer is treated to improve outcomes for patients.”

References

Enhertu approved in the EU as the first HER2 directed therapy for patients with HER2 low metastatic breast cancer. News release. Daiichi Sankyo. January 26, 2023. Accessed January 26, 2023. https://bit.ly/3XYAnRx
ENHERTU® recommended for approval in the EU by CHMP for patients with HER2 low metastatic breast cancer. News release. Daiichi-Sankyo. December 19, 2022. Accessed January 26, 2023. https://bit.ly/3YwJav3