# KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment

Source: https://onco.cc/key-papers/paper-katherine-nejm-2019/  
OnCo record `paper-katherine-nejm-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Women whose HER2-positive breast cancer was still present at surgery after chemotherapy and trastuzumab had half the risk of relapse if their post-surgery treatment was switched to the antibody-drug conjugate T-DM1 instead of continuing trastuzumab.

## Summary

Open-label phase 3 trial of 1,486 patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axilla after neoadjuvant taxane- and trastuzumab-based therapy, randomised to 14 cycles of adjuvant trastuzumab emtansine (T-DM1) or trastuzumab. Primary endpoint was invasive disease-free survival.

Three-year iDFS was 88.3% vs 77.0% (HR 0.50). Later follow-up confirmed an overall survival benefit. It established the response-adapted strategy: treat before surgery, then escalate only for those with residual disease.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2019
- DOI: 10.1056/NEJMoa1814017
- Authors: von Minckwitz G, Huang CS, Mano MS, et al.
- Findings: Three-year invasive disease-free survival 88.3% with T-DM1 vs 77.0% with trastuzumab, an 11.3-point gain; HR 0.50 (95% CI 0.39-0.64).; Distant recurrence as first event 10.5% vs 15.9%.; Benefit was consistent across hormone-receptor status, extent of residual disease, and prior pertuzumab use.; Long-term follow-up confirmed a significant overall survival benefit (HR about 0.66).; More grade 3 or higher adverse events with T-DM1 (25.7% vs 15.4%), notably thrombocytopenia and neuropathy.
- What it means: HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.
- Caveats: Open-label design.; A minority of patients had received pertuzumab before surgery, fewer than in current practice.; Whether adding tucatinib or switching to trastuzumab deruxtecan can further improve outcomes for residual disease is being tested (CompassHER2 RD, DESTINY-Breast05).; Brain metastases as a first site of relapse were not reduced.

## Sources

- NEJM 2019: https://doi.org/10.1056/NEJMoa1814017
- ClinicalTrials.gov NCT01772472: https://clinicaltrials.gov/study/NCT01772472

## Connected records

- ideas: [ADC for residual disease after KEYNOTE-522](https://onco.cc/ideas/idea-post-neoadjuvant-adc/), [Sequencing HER2 ADCs by payload after T-DXd](https://onco.cc/ideas/idea-her2-adc-sequencing-payload/)
- cancers: [Early HER2-positive breast cancer](https://onco.cc/cancers/her2-positive-early-breast-cancer/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- trials: [DESTINY-Breast03](https://onco.cc/trials/destiny-breast03/), [DESTINY-Breast11](https://onco.cc/trials/destiny-breast11/), [KATHERINE](https://onco.cc/trials/katherine/)
- people: [Charles E. Geyer Jr.](https://onco.cc/people/charles-geyer/), [Eleftherios P. Mamounas](https://onco.cc/people/eleftherios-mamounas/), [Gunter von Minckwitz](https://onco.cc/people/gunter-von-minckwitz/), [Sibylle Loibl](https://onco.cc/people/sibylle-loibl/), [Zhi-Ming Shao](https://onco.cc/people/shao-zhi-ming/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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