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