New Protocol: Tucatinib with Trastuzumab and Pertuzumab for Maintenance in HER2-Positive Breast Cancer

The study found that adding tucatinib to trastuzumab and pertuzumab significantly improved progression-free survival compared with placebo, with a hazard ratio of 0.641. Tucatinib showed a consistent benefit across patient subgroups, including those with brain metastases. Despite the efficacy, treatment-emergent adverse events were higher in the tucatinib arm, with a notable increase in elevated liver enzymes.

Study

Randomized, double-blind, placebo-controlled, international, phase III trial [HER2CLIMB-05]

First-line maintenance therapy for HER2-positive metastatic breast cancer after taxane-trastuzumab-pertuzumab

Tucatinib (n=326) vs placebo (n=328) in combination with trastuzumab and pertuzumab

Efficacy

mPFS: 24.9 mos vs 16.3 mos (tucatinib vs. placebo) (HR 0.641 [0.514-0.799])

Safety

Grade >=3 TEAEs: diarrhea (6.1% vs 4.0%), elevated ALT (13.5% vs 0.6%), elevated AST (7.1% vs 0.6%)

Serious TEAEs: 16.9% vs 8.0%

Treatment discontinuation due to TEAEs: 13.5% vs 4.6%

J Clin Oncol. Published online December 10, 2025

Dieras V, Curigliano G, Martin M HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2 Metastatic Breast Cancer

http://doi.org/10.1200/JCO-25-02600

Reviewed by Ulas D. Bayraktar, MD on Jan 21, 2026