TH3RESA
In HER2-positive advanced breast cancer previously treated with trastuzumab, lapatinib and a taxane, does T-DM1 improve survival versus physician's-choice therapy?
Trial design and population
602 patients with HER2-positive advanced breast cancer previously treated with trastuzumab, lapatinib and a taxane, with progression on ≥2 HER2-directed regimens in advanced disease.
Trastuzumab emtansine (T-DM1) 3.6 mg/kg IV every 3 weeks vs physician's-choice therapy; crossover to T-DM1 allowed after progression.
602
Overall survival
Key results
Final median OS was 22.7 months with T-DM1 vs 15.8 months with physician's choice (HR 0.68, 95% CI 0.54–0.85; P=.0007), despite 47% crossover from control to T-DM1. Grade ≥3 AEs occurred in 40% vs 47%.
Source-reported outcome visualization
Median overall survival · Final analysis
Source-reported endpoint and unit. Median survival is not converted into an NNT.
Absolute Effect
Median OS difference 6.9 months is not an NNT; crossover likely attenuated the OS contrast.
NNT: Not calculated; median OS difference is not a valid NNT. Do not convert median survival differences into NNT.
NNH: Not quantifiable. T-DM1 increases thrombocytopenia and haemorrhage; hepatotoxicity and rare nodular regenerative hyperplasia require monitoring. Grade ≥3 AEs were 40% vs 47%.
Safety and treatment burden
T-DM1 increases thrombocytopenia and haemorrhage; hepatotoxicity and rare nodular regenerative hyperplasia require monitoring. Grade ≥3 AEs were 40% vs 47%.
Follow-up, maturity and limitations
Final OS analysis.
Predates trastuzumab deruxtecan and tucatinib-based treatment. Current sequence differs, but TH3RESA is foundational evidence for T-DM1 after multiple HER2 therapies.
Clinical interpretation
Current-practice context · reviewed 20 October 2026
Historical evidence is separated from current sequencing. Confirm current guidelines, local regulatory status, biomarkers, prior therapies and patient-specific contraindications. Newer treatments may have changed the preferred sequence; where NNT/NNH cannot be defensibly quantified, no surrogate calculation is made.