AstraZeneca (LSE:AZN) announced US FDA approvals for Enhertu in the neoadjuvant setting (Enhertu followed by taxane, trastuzumab and pertuzumab, THP) for Stage II-III HER2‑positive breast cancer and in the adjuvant setting for patients with residual invasive disease following trastuzumab (with or without pertuzumab) and taxane‑based treatment.
The approvals move Enhertu into curative‑intent early disease and follow positive Phase III data from DESTINY‑Breast11 (neoadjuvant) and DESTINY‑Breast05 (adjuvant), presented at ESMO 2025 and published in Annals of Oncology and NEJM.
Under the March 2019 global collaboration, Daiichi Sankyo co‑develops and co‑commercialises Enhertu with AstraZeneca, is responsible for manufacturing and supply, and will recognise US sales.
AstraZeneca must pay Daiichi Sankyo $155 million in milestone payments following these US approvals.
DESTINY‑Breast11 reported a pathologic complete response rate of 67.3% with Enhertu→THP versus 56.3% with ddAC‑THP (absolute improvement 11.2%, p=0.003), and DESTINY‑Breast05 showed a 53% reduction in risk of invasive disease recurrence or death (IDFS HR 0.47, p<0.0001) with three‑year IDFS 92.4% versus 83.7%.
Safety readouts showed no new concerns overall but higher adjudicated ILD/pneumonitis in DESTINY‑Breast05 (9.6% with Enhertu versus 1.6% with T‑DM1), including seven Grade 3 events and two Grade 5 events in the Enhertu arm, while DESTINY‑Breast11 reported similar overall drug‑related AEs and lower rates of high‑grade toxicities versus ddAC‑THP.
Both US submissions were reviewed under Project Orbis, DESTINY‑Breast05 previously received Priority Review and Breakthrough Therapy Designation, and separate regulatory applications are under review in other countries.
"These approvals mark an important step forward, expanding the possibility of cure to more patients for the first time in many years and positioning Enhertu as a foundational treatment in early breast cancer," said Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca.
