TY - JOUR
T1 - Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer
T2 - primary analysis of the randomized phase III trial HER2CLIMB-02☆
AU - HER2CLIMB-02 study investigators
AU - Hurvitz, S. A.
AU - Loi, S.
AU - O’Shaughnessy, J.
AU - Okines, A. F.C.
AU - Tolaney, S. M.
AU - Sohn, J.
AU - Saura, C.
AU - Zhu, X.
AU - Cameron, D.
AU - Bachelot, T.
AU - Hamilton, E.
AU - Curigliano, G.
AU - Wolff, A. C.
AU - Harbeck, N.
AU - Masuda, N.
AU - Vahdat, L.
AU - Zaman, K.
AU - Valdes-Albini, F.
AU - Block, M.
AU - Pluard, T.
AU - Tan, T. J.
AU - Gawryletz, C.
AU - Chan, A.
AU - Bedard, P. L.
AU - Yerushalmi, R.
AU - Xu, B.
AU - Schmitt, M.
AU - Xie, D.
AU - Borges, V. F.
AU - Beecroft, Claire
AU - Boyle, Frances
AU - Dinh, Phuong
AU - Loi, Sherene
AU - Yeo, Belinda
AU - Egle, Daniel
AU - Strasser-Weippl, Kathrin
AU - Canon, Jean Luc
AU - Gombos, Andrea
AU - Nuytemans, Laure
AU - Papadimitriou, Konstantinos
AU - Rorive, Andree
AU - Taylor, Donatienne
AU - Wildiers, Hans
AU - Ayoub, Jean Pierre
AU - Bedard, Philippe
AU - Doyle, Catherine
AU - Lohmann, Ana
AU - Song, Xinni
AU - Zhu, Xiaofu
AU - Stopeck, Alison
N1 - Publisher Copyright:
© 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2026/3
Y1 - 2026/3
N2 - 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.
AB - 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.
KW - advanced/metastatic breast cancer
KW - brain metastases
KW - human epidermal growth factor receptor 2-positive
KW - T-DM1
KW - trastuzumab emtansine
KW - tucatinib
UR - https://www.scopus.com/pages/publications/105030211403
U2 - 10.1016/j.annonc.2025.11.005
DO - 10.1016/j.annonc.2025.11.005
M3 - Article
C2 - 41260264
AN - SCOPUS:105030211403
SN - 0923-7534
VL - 37
SP - 341
EP - 352
JO - Annals of Oncology
JF - Annals of Oncology
IS - 3
ER -