Clinical Summary:

• Design/Population: The phase 3 HER2CLIMB-02 trial randomized previously treated patients with HER2-positive locally advanced or metastatic breast cancer, including those with brain metastases, to receive T-DM1 with either tucatinib or placebo.
• Key Outcomes: At analysis, the addition of tucatinib improved progression-free survival however, overall survival was similar between arms. 
• Clinical Relevance: Tucatinib continues to provide disease control benefit in combination with T-DM1, supporting its role in previously treated patients with HER2-positive breast cancer.

Final results from the phase 3 HER2CLIMB-02 trial showed that adding tucatinib to trastuzumab emtansine (T-DM1) prolongs progression-free survival (PFS) among previously treated patients with HER2-positive locally advanced or metastatic breast cancer, including those with brain metastases.

These results were presented by Giuseppe Curigliano, MD, Istituto Europeo di Oncologia IRCCS, Milan, Italy, at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress in Berlin, Germany.

In this study, 463 patients previously treated with trastuzumab and a taxane, including 204 patients with brain metastases, were randomized 1:1 to receive 3.6 mg/kg of T-DM1 once every 21 days with either 300 mg of tucatinib (n = 228; brain metastases n = 99) or placebo (n = 235; brain metastases n = 105). The primary end point was overall survival (OS). A key exploratory end point was PFS. Outcomes were evaluated in both the intention-to-treat population and in patients with brain metastases. 

At a median follow-up of 50.7 months, median OS was 43.3 months in the T-DM1 plus tucatinib arm and 41 months in the T-DM1 plus placebo arm (hazard ratio [HR], 0.983; P = .8959). Median PFS was 9.5 months and 7.4 months, respectively. Among patients with brain metastases, median OS was 35.8 months in the T-DM1 plus tucatinib arm and 34.4 months in the T-DM1 plus placebo arm, and median PFS was 7.8 months and 5.7 months, respectively. 

The rate of subsequent anticancer therapy was 83.7% in the T-DM1 plus tucatinib arm and 87.8% in the T-DM1 plus placebo arm. 

“The final analysis confirmed a PFS benefit of adding [tucatinib] to T-DM1 in [patients] with previously treated [HER2-positive locally advanced or metastatic breast cancer], including those with [brain metastases],” concluded Dr Curigliano. “OS did not differ significantly between treatment arms.” 

Source:

Curigliano G, Borges V, O’Shaughnessy JA, et al. Addition of tucatinib to trastuzumab emtansine (T-DM1) in patients with previously treated HER2+ locally advanced/metastatic breast cancer (LA/MBC): Updated efficacy analysis from the HER2CLIMB-02 trial. Presented at European Society for Medical Oncology (ESMO) Breast Cancer Congress; March 6 - 8, 2026; Berlin, Germany. 423RO.