The HER2CLIMB-05 phase III trial demonstrated that adding tucatinib to trastuzumab and pertuzumab as first-line maintenance therapy significantly improved progression-free survival by 36% compared to trastuzumab and pertuzumab alone in patients with HER2-positive metastatic breast cancer. The benefit was observed regardless of brain metastases or hormone receptor status, with manageable adverse effects including diarrhea and elevated liver enzymes.
Study
|
Randomized, double-blind, placebo-controlled, international, phase III trial [HER2CLIMB-05; NCT05132582] |
| HER2-positive metastatic breast cancer without evidence of progression post induction therapy (paclitaxel + TP) |
| Tucatinib (300 mg, n=326) vs placebo (n=328) twice daily combined with trastuzumab and pertuzumab (TP)
|
Efficacy
|
mPFS: 24.9 mos vs 16.3 mos (tucatinib + TP vs. placebo + TP) (HR 0.641 [0.514-0.799]) |
| mOS: Not reached in either arm (HR 0.539 [0.303-0.957], immature data)
|
Safety
|
Grade >=3 adverse events: diarrhea (6.1% vs 4.0%), elevated ALT (13.5% vs 0.6%) |
| Serious AEs: elevated ALT (1.5% vs 0%), drug-induced liver injury (1.2% vs 0%)
|
J Clin Oncol 2025;44:1597-1607
http://doi.org/10.1200/JCO-25-02600
Reviewed by Ulas D. Bayraktar, MD on Jun 15, 2026
