In HER2-positive breast cancer, drugs are usually given before surgery. If some tumour is still left at surgery after that, the risk of the cancer coming back is higher, and until now the standard treatment after surgery was the drug T-DM1 (Kadcyla). In DESTINY-Breast05, trastuzumab deruxtecan (Enhertu) cut the risk of the cancer coming back or death by about half compared with T-DM1: after 3 years, about 92 of every 100 patients on Enhertu were free of the cancer coming back, versus about 84 with T-DM1. Nausea was common, and lung inflammation is a serious side effect that needs regular follow-up.
High-risk HER2-positive with residual invasive disease after neoadjuvant therapy
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | 5.4 mg/kg | IV (do not dilute with sodium chloride solution) | Day 1 |
ILD: in the adjuvant setting, rule out radiation pneumonitis.
On the page “Breast cancer” · Early HER2-positive disease: before and after surgery
HER2-positive breast cancer with residual invasive disease after neoadjuvant trastuzumab (± pertuzumab) and a taxane
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (Enhertu) | 5.4 mg/kg | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
In the adjuvant setting, when ILD is suspected, rule out radiation pneumonitis; if only radiation pneumonitis is likely, consider holding for grade 2 and stop permanently for grade 3 or higher.
On the page “Trastuzumab deruxtecan (Enhertu)” · Dose and schedule (FDA label)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Trastuzumab deruxtecan 5.4 mg per kg, IV infusion on day 1 of each 21-day cycle, for up to 14 cycles or until disease recurrence or unacceptable toxicity.
Trastuzumab emtansine 3.6 mg per kg, IV infusion on day 1 of each 21-day cycle, for up to 14 cycles or until disease recurrence or unacceptable toxicity.
Source of the regimen details: FDA label for Enhertu (ENHERTU, 2026-05 version, sections 2 and 14); ClinicalTrials.gov NCT04622319; abstract of the paper (5.4 and 3.6 mg per kg).
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with high-risk HER2-positive breast cancer who had residual invasive disease at surgery after neoadjuvant therapy and either node-positive disease at surgery or inoperable disease at diagnosis.
Primary endpoint: invasive disease-free survival (IDFS).
Key secondary endpoint: disease-free survival (DFS; including non-invasive breast cancers and second primary non-breast cancers). Other endpoints: overall survival, distant recurrence-free interval, brain metastasis-free interval and safety.
Most common adverse events with trastuzumab deruxtecan: nausea (71.3%), constipation (32.0%), decreased neutrophil count (31.6%) and vomiting (31.0%). With trastuzumab emtansine: increased liver enzymes (AST in 50.2% and ALT in 45.3%) and decreased platelet count (49.8%). Drug-related interstitial lung disease was more frequent with trastuzumab deruxtecan (9.6% versus 1.6%), and two patients in the trastuzumab deruxtecan group died of it.
On 15 May 2026 the FDA approved trastuzumab deruxtecan as adjuvant treatment for adults with HER2-positive breast cancer with residual invasive disease after trastuzumab-based (with or without pertuzumab) and taxane neoadjuvant therapy (5.4 mg per kg every 3 weeks for 14 cycles). This study makes T-DXd the replacement for T-DM1 (the previous standard based on KATHERINE) in high-risk patients with residual disease.
The trial was open-label. Follow-up (median about 30 months) is short for assessing overall survival. Only high-risk patients (node involvement after neoadjuvant therapy or inoperable disease at diagnosis) were enrolled. Interstitial lung disease with fatal outcome occurred, and patients receiving concurrent radiotherapy need pulmonary monitoring. An erratum to the paper was published in April 2026.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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