Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02
Published report from the HER2CLIMB-02 trial registered as NCT03975647, in Annals of Oncology (2026), chosen as the most cited paper whose own text cites the registry id.
Overview
Background: Trastuzumab emtansine (T-DM1) is a standard treatment option in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (LA/MBC). Here, we report the efficacy and safety of tucatinib in combination with T-DM1 compared with T-DM1 alone from the phase III HER2CLIMB-02 study (NCT03975647).
Patients and methods: Eligible patients had HER2-positive LA/MBC that had been previously treated with trastuzumab and a taxane in any setting; these included patients with brain metastases (BMs). Patients were randomly assigned 1: 1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm.
Results: In total, 463 patients were randomly assigned. After a median follow-up duration of 24.4 months, the median progression-free survival (PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.61-0.95, P = 0.0163]. A PFS benefit was observed across all prespecified subgroups, including in patients with BMs. Interim overall survival analysis results were immature. The median OS was not reached in the tucatinib arm and was 38.0 months in the control arm (HR 1.23, 95% CI 0.87-1.74). The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively). The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm).
Conclusion: The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2-positive LA/MBC, including patients with BMs, and exhibited a manageable safety profile.
Indexed on Europe PMC as PubMed record 41260264 (DOI 10.1016/j.annonc.2025.11.005). Its abstract cites the registry id NCT03975647, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT03975647 with the most citations, so it is the natural first reading for anyone following the HER2CLIMB-02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.