AstraZeneca PLC (NASDAQ: AZN) and Daiichi Sankyo (TYO: 4568) released the latest data supporting the antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) as a new standard of care for breast cancer. An update from the DESTINY-Breast03 Phase III study assessing Enhertu head-to-head against Roche’s Kadcyla (trastuzumab emtansine, TDM-1) in patients with previously treated HER2-positive metastatic breast cancer found that Enhertu produced a significant improvement in overall survival (OS), with a 36% reduction in risk of death (HR 0.64; 95% CI 0.47-0.87; p=0.0037).
Consistent Survival Benefits Across Subgroups
As noted in the release, the survival benefit was consistent across all analyzed subgroups, including patients with or without baseline brain metastases, with or without baseline visceral disease, those who were hormone receptor (HR)-positive or HR-negative, and regardless of prior pertuzumab or lines of systemic therapy.
Study Details and Results
The DESTINY-Breast03 study (NCT03529110) was initiated in 2018 and enrolled over 500 patients at 164 sites, including 12 in mainland China. The primary endpoint was progression-free survival (PFS), with AZ and Daiichi announcing earlier this year that Enhertu produced a 22-month PFS improvement versus Kadcyla at the interim readout stage. The latest analysis confirmed those findings, with the median PFS readout at 28.8 months for Enhertu versus 6.8 months. The objective response rate (ORR) was 78.5%, including 21.1% with a complete response (CR) in the Enhertu arm, versus an ORR of 35.0% and 9.5% CR rate for Kadcyla. Finally, the median duration of response (DoR) was 36.6 months for Enhertu versus 23.8 months for Kadcyla.
Enhertu’s Regulatory Approvals and Future Prospects
Enhertu has secured five indication approvals in the United States to date: as a third-line therapy for HER2-positive breast cancer (BC) in December 2019; for previously treated HER2-positive gastric cancer in January 2021; for previously HER2-treated HER2-positive BC in May 2022; for previously treated HER2-low BC in August 2022; and for previously treated HER2-positive non-small cell lung cancer in August 2022. The drug has yet to be approved in China, but is currently under review for at least two indications, including HER2-low BC.-Fineline Info & Tech
