HER2CLIMB
In heavily pretreated HER2-positive metastatic breast cancer, including brain metastases, does tucatinib added to trastuzumab–capecitabine improve outcomes?
Trial design and population
612 patients previously treated with trastuzumab, pertuzumab and T-DM1; stable or active brain metastases were eligible.
Tucatinib 300 mg orally twice daily plus trastuzumab and capecitabine vs placebo plus trastuzumab and capecitabine.
612
PFS; OS key secondary endpoint
Key results
Updated median OS was 24.7 vs 19.2 months (HR 0.73, 95% CI 0.59–0.90); primary-analysis median PFS was 7.8 vs 5.6 months (HR 0.54, 95% CI 0.42–0.71). Benefit was seen in patients with brain metastases.
Source-reported outcome visualization
Median overall survival · Updated median
Source-reported endpoint and unit; median survival is not converted into an NNT.
Absolute Effect
Median OS difference 5.5 months is not an NNT. CNS activity is a major clinically relevant finding.
NNT: Not calculated; median OS difference is not a valid NNT. Endpoint/time horizon are stated above; do not convert median survival differences into NNT.
NNH: Not quantifiable. Grade ≥3 diarrhoea and aminotransferase elevation are important; capecitabine causes hand-foot syndrome. Diarrhoea, hepatotoxicity and drug interactions require monitoring.
Safety and treatment burden
Grade ≥3 diarrhoea and aminotransferase elevation are important; capecitabine causes hand-foot syndrome. Diarrhoea, hepatotoxicity and drug interactions require monitoring.
Follow-up, maturity and limitations
Updated survival analyses with multi-year follow-up.
Evidence follows prior trastuzumab, pertuzumab and T-DM1. Modern sequencing often places trastuzumab deruxtecan earlier, but inclusion of active brain metastases remains distinctive.
Clinical interpretation
Current-practice context · reviewed 20 October 2026
Historical evidence is separated from current sequencing. Confirm local regulatory status, current guidelines, biomarkers, prior therapies and patient-specific contraindications before applying these results. Newer treatments may have changed the preferred sequence; where NNT/NNH cannot be defensibly quantified, no surrogate calculation is made.