In the HER2CLIMB-02 trial, the addition of tucatinib to T-DM1 improved progression-free survival among patients with HER2-positive breast cancer, showing an increase from 7.4 to 9.5 months. The regimen was associated with higher rates of liver enzyme elevations but was overall manageable. The overall survival results were immature.
Study
|
Randomized, double-blind, placebo-controlled, phase III trial [HER2CLIMB-02] |
| Previously treated HER2-positive locally advanced or metastatic breast cancer |
| Tucatinib plus T-DM1 (n=228) vs placebo plus T-DM1 (n=235)
|
Efficacy
|
ORR: 42% vs 36% |
| mPFS: 9.5 mos vs 7.4 mos (HR 0.76 [0.61-0.95]) |
| mOS: Not reached vs 38.0 mos (HR 1.23 [0.87-1.74])
|
Safety
|
Grade >=3 AEs: 68.8% vs 41.2% |
| AST increased (16.5% vs 2.6%), ALT increased (16.5% vs 2.6%) |
| TEAEs leading to discontinuation: 22.1% vs 11.6%
|
Ann Oncol. Published online 2025.
http://doi.org/10.1016/j.annonc.2025.11.005
Reviewed by Ulas D. Bayraktar, MD on Dec 8, 2025
