Tucatinib: Chemo-Sparing Maintenance for HER2+ Metastatic Breast Cancer

Erika P. Hamilton, MD, Sarah Cannon Research Institute, provides an overview of the phase 3 HER2CLIMB-05 trial (NCT05132582), the results of which were presented at the 2025 San Antonio Breast Cancer Symposium.¹ The randomized, double-blind trial investigated the addition of tucatinib (Tukysa) to trastuzumab (Herceptin) and pertuzumab (Perjeta; HP) to first-line maintenance therapy for patients with HER2-positive (HER2+) metastatic breast cancer.

The study enrolled almost 700 women with HER2+ disease. Enrollment included both hormone receptor (HR)-positive and HR-negative patients, and those who were HR-positive were allowed to receive endocrine therapy in the maintenance portion of both arms. Of note, criteria only included patients who showed no progression on 4–8 cycles of prior first-line standard-of-care treatment.

HER2CLIMB-05 successfully met its primary endpoint of progression-free survival (PFS), with the addition of tucatinib prolonging PFS by 8.6 months. This shifted the expected PFS from roughly 18 months to over 24 months. According to Dr Hamilton, the results were highly clinically meaningful and statistically significant.

The central conclusion from HER2CLIMB-05 is that adding tucatinib to HP maintenancewith or without endocrine therapywas beneficial for patients, regardless of their hormone receptor status. This not only lengthens PFS in the first-line maintenance setting but also offers patients an option to increase the time they are off cytotoxic chemotherapy.

When contextualizing these results, Dr Hamilton emphasizes that it is important to remember that the reported PFS reflects only the maintenance phase and does not include the initial induction chemotherapy regimen.

REFERENCES

1. Hamilton E, Curigliano G, Martin M, et al. HER2CLIMB-05: A randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-01.