Clinical trialPhase 3Breast cancer

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

N Engl J Med · 20191486 patients

von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. N Engl J Med. 2019. 380:617-628

A newer report of this study has been published: Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer (2025)

Study type: Clinical trial
Study name: KATHERINE
Phase: Phase 3
Design: Randomised, open-label trial
Sample size: 1486 patients
Source: N Engl J Med · 2019
Trial registration: NCT01772472

In plain words

In HER2-positive breast cancer, if some tumour is still left after the treatment given before surgery, replacing trastuzumab with T-DM1 (an "antibody–drug conjugate") after surgery halved the risk of the disease coming back, and over 8 years of follow-up it also raised the chance of being alive.

Key results

88.3% vs 77.0%

3-year iDFS

HR 0.50 (95% CI 0.39–0.64); P<0.001

80.8% vs 67.1%

7-year iDFS (final analysis)

HR 0.54 (95% CI 0.44–0.66); NEJM 2025, median follow-up 8.4 years

89.1% vs 84.4%

7-year overall survival

HR 0.66 (95% CI 0.51–0.87); P=0.003; NEJM 2025

Drugs in this study:Trastuzumab (Herceptin)Trastuzumab emtansine (Kadcyla)

Dose and schedule cards

Adjuvant T-DM1 (KATHERINE)

HER2-positive with residual invasive disease after neoadjuvant therapy containing a taxane and trastuzumabCycle length: Every 21 daysOn the page “Breast cancer” · Early HER2-positive disease: before and after surgery

HER2-positive with residual invasive disease after neoadjuvant therapy containing a taxane and trastuzumab

Drug	Dose	Route	Schedule
Trastuzumab emtansine (T-DM1)	3.6 mg/kg (do not exceed this dose)	IV; first infusion over 90 min, subsequent infusions over 30 min	Day 1

Cycle length: Every 21 days
Duration: 14 cycles, unless recurrence or unmanageable toxicity

Dose reduction: 3 and then 2.4 mg/kg; do not re-escalate after a reduction. Monitoring: liver enzymes and bilirubin, platelets, LVEF; discontinue permanently for ILD/pneumonitis; for grade 3–4 neuropathy, withhold until grade 2 or lower. Observe for 90 minutes after the first infusion and for 30 minutes after subsequent infusions.

On the page “Breast cancer” · Early HER2-positive disease: before and after surgery

Early breast cancer with residual disease (KATHERINE)

HER2-positive, residual invasive disease after neoadjuvant treatment with a taxane and trastuzumabOn the page “Trastuzumab emtansine (Kadcyla)” · Dose and schedule (FDA label)

HER2-positive, residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab

Drug	Dose	Route	Schedule
Trastuzumab emtansine (Kadcyla)	3.6 mg/kg (never more)	IV infusion; initial 90 minutes, then 30 minutes if tolerated	Day 1

Cycle length: Every 3 weeks (21 days)
Duration: 14 cycles in total, unless recurrence or unmanageable toxicity

On the page “Trastuzumab emtansine (Kadcyla)” · Dose and schedule (FDA label)

T-DM1

HER2-positive breast cancer: residual disease (adjuvant) or metastatic diseaseCycle length: Every 21 daysOn the page “Trastuzumab emtansine (T-DM1, Kadcyla): dose and schedule”

HER2-positive breast cancer: residual disease (adjuvant) or metastatic disease

Drug	Dose	Route	Schedule
Trastuzumab emtansine	3.6 mg/kg	IV (first dose over 90 minutes, then 30 minutes)	Day 1

Cycle length: Every 21 days
Duration: Adjuvant: 14 cycles; metastatic: until progression

Dose reduction: 3 mg/kg, then 2.4; below that, stop.

Dose source:.

On the page “Trastuzumab emtansine (T-DM1, Kadcyla): dose and schedule”

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.

Treatment arms and regimens

1T-DM1 (743 patients)

Trastuzumab emtansine (T-DM1) 3.6 mg/kg IV every 3 weeks for 14 cycles.

2Trastuzumab (743 patients)

Trastuzumab 6 mg/kg IV every 3 weeks for 14 cycles.

Source of the regimen details: ClinicalTrials.gov NCT01772472 (T-DM1 3.6 mg/kg and trastuzumab 6 mg/kg every 3 weeks, 14 cycles)

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.

Study population

Patients with early HER2-positive breast cancer who had residual invasive disease in the breast or axilla at surgery after neoadjuvant therapy containing a taxane (± anthracycline) and trastuzumab.

Endpoints

Primary endpoint: invasive disease-free survival (iDFS). Secondary: distant recurrence-free survival, overall survival, safety.

Safety and side effects

Safety data were consistent with the known profile of T-DM1, which caused more adverse events than trastuzumab alone. In the final analysis, grade 3 or higher adverse events were reported in 26.1% of the T-DM1 group and 15.7% of the trastuzumab group. Thrombocytopenia, raised liver enzymes and peripheral neuropathy are known adverse effects of T-DM1.

Clinical significance and place in guidelines

In May 2019 the FDA approved T-DM1 for adjuvant treatment of residual HER2-positive disease. The final analysis (Geyer et al., NEJM 2025) showed a significant improvement in overall survival. ESMO guideline (Pan-Asian adapted version 2024): patients with residual invasive disease after neoadjuvant therapy should receive adjuvant T-DM1 for up to 14 cycles [I, A]. The newer DESTINY-Breast05 trial (2026) has shown superiority of T-DXd over T-DM1 in high-risk patients with residual disease.

Limitations

Open-label design; most patients had received neoadjuvant therapy without pertuzumab; T-DXd is now a potential alternative in high-risk patients (DESTINY-Breast05).

Original article (DOI)PubMed ClinicalTrials.gov

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.