FDA approves Enhertu for early HER2

The U.S. Food and Drug Administration approved Enhertu on May 15 for two new uses in HER2-positive early breast cancer, moving the antibody-drug conjugate into treatment before surgery and after surgery for selected patients. AstraZeneca and Daiichi Sankyo said the approvals cover neoadjuvant treatment with Enhertu followed by taxane, trastuzumab and pertuzumab for adults with Stage II or Stage III disease, and adjuvant treatment for adults with residual invasive disease after prior trastuzumab-based and taxane-based therapy. (daiichisankyo.com) (astrazeneca.com) The May 15 action extends a drug already used across metastatic HER2-positive and HER2-low breast cancer into curative-intent settings. The companies said the neoadjuvant approval was based on the Phase III DESTINY-Breast11 trial and the adjuvant approval on the Phase III DESTINY-Breast05 trial, with results presented at the 2025 European Society for Medical Oncology Congress and published in *Annals of Oncology* and *The New England Journal of Medicine*. (fda.gov) The FDA had already approved Enhertu with pertuzumab on December 15, 2025, for first-line treatment of unresectable or metastatic HER2-positive breast cancer, also requiring selection by an FDA-approved HER2 test. (astrazeneca.com) ### Which early-stage patients are now eligible for Enhertu? The new neoadjuvant indication applies to adults with HER2-positive Stage II or Stage III breast cancer who receive Enhertu before surgery and then continue with taxane, trastuzumab and pertuzumab. The adjuvant indication applies to adults whose tumors still show residual invasive disease after neoadjuvant trastuzumab, with or without pertuzumab, plus taxane-based treatment. (daiichisankyo.com) FDA and company materials describe HER2-positive disease in these settings through FDA-approved testing, and the earlier metastatic approval specifies HER2 positivity as immunohistochemistry 3+ or in situ hybridization positive. FDA also approved companion diagnostic devices in the metastatic first-line setting alongside the December 2025 decision. (fda.gov) ### What numbers drove the approval before surgery? DESTINY-Breast11 showed a pathologic complete response rate of 67.3% for Enhertu followed by THP, compared with 56.3% for dose-dense doxorubicin and cyclophosphamide followed by THP, according to Daiichi Sankyo. The company said that represented an 11.2 percentage-point difference, with a 95% confidence interval of 3.9 to 18.3 and a p-value of 0.003. (astrazeneca.com) *Annals of Oncology* described DESTINY-Breast11 as a Phase III trial testing neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab and pertuzumab against anthracycline-containing standard therapy in high-risk HER2-positive early-stage breast cancer. (fda.gov) ### What changed for patients after surgery? DESTINY-Breast05 compared Enhertu with trastuzumab emtansine, or T-DM1, in patients with residual invasive disease after neoadjuvant therapy. Daiichi Sankyo said Enhertu reduced the risk of invasive disease recurrence or death by 53%, with a hazard ratio of 0.47 and a p-value below 0.0001. The same trial reported a three-year invasive disease-free survival rate of 92.4% for Enhertu and 83.7% for T-DM1. (daiichisankyo.com) AstraZeneca said in March, when the filing received Priority Review, that the FDA action date was expected in the third quarter of 2026, but the agency approved the application in May. ### Why does HER2 testing matter more now? (annalsofoncology.org) The December 2025 metastatic approval and the new early-stage approvals all tie treatment to HER2-positive disease identified by FDA-approved testing. FDA said companion diagnostic devices were approved with the first-line metastatic indication to select patients for Enhertu plus pertuzumab. (daiichisankyo.com) Shanu Modi of Memorial Sloan Kettering Cancer Center said in AstraZeneca’s release that the neoadjuvant setting offers the earliest chance to improve outcomes and that the adjuvant setting gives another chance to prevent recurrence in patients with residual disease after surgery. Her comments were included in the companies’ announcement of the May 15 approvals. (daiichisankyo.com) ### What safety issues remain on the label? Enhertu’s prescribing information carries a boxed warning for interstitial lung disease and embryo-fetal toxicity. The label says interstitial lung disease and pneumonitis, including fatal cases, have been reported and that the drug must be permanently discontinued in patients with Grade 2 or higher ILD or pneumonitis. (fda.gov) The FDA’s December 2025 approval notice for the metastatic first-line use also listed warnings and precautions for neutropenia and left ventricular dysfunction. Those risks remain part of the treatment discussion as use broadens across earlier lines of therapy. (astrazeneca.com) ### What is the next concrete step for doctors and patients? Drugs@FDA materials and the updated Enhertu label now set out the approved early-stage and metastatic uses, dosing and warnings for U.S. clinicians. AstraZeneca and Daiichi Sankyo said the two early-stage approvals were based on DESTINY-Breast11 and DESTINY-Breast05, and the FDA’s posted prescribing information will guide how treatment and HER2 testing are sequenced in practice. (accessdata.fda.gov) (daiichisankyo.com) (fda.gov)