Tucatinib, combined with trastuzumab and pertuzumab (HP), showed clinically meaningful efficacy in patients with HER2 positive metastatic breast cancer, according to new research presented at the 2026 ASCO Annual Meeting.

HER2-positive metastatic breast cancer is typically managed with chemotherapy-based induction followed by maintenance therapy. The phase 3 HER2CLIMB-05 trial investigated whether adding tucatinib — an oral HER2-targeted TKI — to maintenance HP could extend progression-free survival (PFS) across key patient subgroups.

Patients with HER2+ metastatic breast cancer who had not progressed after taxane plus HP induction were randomly assigned 1:1 to tucatinib 300 mg twice daily or placebo, both combined with maintenance HP. Endocrine therapy was permitted for hormone receptor-positive patients.

Approximately 654 patients were randomized. The population was stratified by three factors: de novo vs recurrent diagnosis, hormone receptor status, and presence or history of brain metastases. Overall, 69% had de novo disease, 53% were hormone receptor-positive, and 12% had baseline brain metastases.

The primary endpoint was investigator-assessed PFS. Across the overall population, tucatinib plus HP significantly improved PFS vs placebo plus HP. The benefit was consistent across all subgroups.

Confirmed objective response rates also favored tucatinib across all subgroups — 22.6% vs 15.2% overall. Median duration of response was 20.9 vs 16.9 months, with benefit seen regardless of hormone receptor status, de novo vs recurrent disease, or history of brain metastases.

Safety profiles across subgroups were consistent with the overall trial population. No new safety signals were identified, supporting the tolerability of tucatinib added to maintenance HP across a diverse patient population.

“Results were consistent with the overall population and support [tucatinib and trastuzumab and pertuzumab] as a potential new maintenance therapy across pts with HER2+ metastatic breast cancer.”

- Study author Erika Hamilton, MD, Breast Cancer Research Program, Sarah Cannon Research Institute, Nashville, Tennessee.

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References:

https://www.asco.org/abstracts-presentations/259336

https://clinicaltrials.gov/study/NCT05132582

Disclosures: Some authors declared relevant financial disclosures. See full abstract for details. Pfizer Inc. supported the study.

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