VJToday

FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer

On October 7, 2026, the U.S. Food and Drug Administration (FDA) approved tucatinib in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction therapy.¹ Although first-line induction with trastuzumab, pertuzumab and a taxane can achieve substantial tumour control, disease progression remains common, highlighting the need for maintenance strategies that can prolong remission while maintaining HER2 pathway suppression.2

The approval was supported by findings from the Phase III HER2CLIMB-05 trial (NCT05132582), which evaluated tucatinib or placebo combined with trastuzumab and pertuzumab in patients whose disease had not progressed following 4-8 cycles of induction treatment. Efficacy was assessed in 654 patients, including those with or without brain metastases. In this randomized, double-blind, placebo-controlled trial, the primary endpoint of investigator-assessed progression-free survival (PFS) was significantly improved (HR 0.64, 95% CI: 0.51–0.80), with median PFS of 24.9 months compared with 16.3 months for trastuzumab and pertuzumab alone. The PFS benefit was consistent across prespecified subgroups, including patients with and without baseline brain metastases and irrespective of hormone receptor status. The safety profile was consistent with the known effects of tucatinib, with diarrhea, nausea, and elevated liver enzymes among the most common adverse events. Overall survival data remain immature.2

Erika Hamilton, MD, Sarah Cannon Research Institute, Nashville, TN, who presented the data at the San Antonio Breast Cancer Symposium (SABCS) 2025 Meeting, summarizes the trial findings, stating that:

“In summary, HER2CLIMB-05 was a positive study. It showed that adding tucatinib for both HR positive as well as HR-negative metastatic HER2-positive patients in the first line, not only prolonged progression-free survival, but also prolonged time off cytotoxic chemotherapy for these patients.”

This approval offers a new maintenance option for HER2-positive metastatic breast cancer, extending disease control after induction while keeping patients off cytotoxic chemotherapy for longer.

References

  1. U.S. Food and Drug Administration. FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer. Available here. (Last Accessed 08/10/2026).
  2. Dieras V, Curigliano G, Martin M, et al. 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. J Clin Oncol 2026;44(17):1597–607.