Clinical trialPhase 3Breast cancer

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer

N Engl J Med · 2025Number of patients not stated in the abstract

Geyer CE, Untch M, Huang CS, Mano MS, Mamounas EP, Wolmark N, et al. N Engl J Med. 2025. 392:249-257

Study type: Clinical trial
Study name: KATHERINE
Phase: Phase 3
Design: Randomised, open-label trial; prespecified final analysis of invasive disease-free survival and second interim analysis of overall survival
Sample size: Number of patients not stated in the abstract
Source: N Engl J Med · 2025
Trial registration: NCT01772472

In plain words

This study looked at people with HER2-positive breast cancer who still had some invasive disease in the tissue removed at surgery after the treatment given before the operation. After about 8 years of follow-up, patients who received the drug trastuzumab emtansine (T-DM1) were more likely to be alive, and less likely to have their disease come back, than patients who received trastuzumab alone. On the other hand, more serious side effects were more common in the T-DM1 group. Treatment decisions should be made with your doctor.

Key results

8.4 years

Median follow-up

0.54 (95% CI 0.44–0.66) in favour of T-DM1

Invasive disease-free survival (unstratified hazard ratio for invasive disease or death)

Versus trastuzumab

80.8% vs 67.1%

7-year invasive disease-free survival

Difference 13.7 percentage points; T-DM1 vs trastuzumab

0.66 (95% CI 0.51–0.87)

Overall survival (unstratified hazard ratio for death)

P = 0.003

89.1% vs 84.4%

7-year overall survival

Difference 4.7 percentage points; T-DM1 vs trastuzumab

26.1% vs 15.7%

Grade 3 or higher adverse events

T-DM1 vs trastuzumab

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

1Trastuzumab emtansine (T-DM1) group

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

2Trastuzumab group

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 IV 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 after neoadjuvant systemic therapy including taxane-based chemotherapy and trastuzumab.

Endpoints

Prespecified final analysis of invasive disease-free survival and second interim analysis of overall survival.

Safety and side effects

Grade 3 or higher adverse events were reported in 26.1% of patients in the T-DM1 group and 15.7% of patients in the trastuzumab group. Details of the types of adverse events are not given in the abstract.

Clinical significance and place in guidelines

This final analysis shows that the superiority of adjuvant T-DM1 over trastuzumab in HER2-positive patients with residual invasive disease after neoadjuvant therapy is durable for invasive disease-free survival and is now also accompanied by improved overall survival. These findings support the use of T-DM1 in this group of patients; however, the higher risk of grade 3 or higher adverse events should be taken into account. The status of approvals and formal guideline recommendations should be checked separately, as they are not stated in the abstract.

Limitations

According to the abstract, the trial was open-label. The overall survival analysis was a second interim analysis. Grade 3 or higher adverse events were more common in the T-DM1 group. Other limitations are not stated in the abstract and should be checked in the full text.

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.