The U.S. Food and Drug Administration (FDA) has approved tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment. The approval, announced October 7, 2026, provides a new option to help keep cancer from growing after initial treatment.
The approval was based on the phase 3 HER2CLIMB-05 clinical trial, which showed that adding tucatinib to trastuzumab and pertuzumab helped patients live longer without their cancer worsening than trastuzumab and pertuzumab alone.
What is maintenance treatment?
Maintenance treatment is ongoing therapy given after initial, or induction, treatment to help keep cancer under control. In HER2CLIMB-05, patients first received trastuzumab, pertuzumab, and a taxane chemotherapy drug. Patients whose cancer had not progressed then received maintenance treatment with trastuzumab and pertuzumab, with either tucatinib or a placebo. This approach allows treatment to continue without the taxane chemotherapy used during induction.
What did HER2CLIMB-05 study?
HER2CLIMB-05 enrolled 654 adults with HER2-positive, unresectable locally advanced or metastatic breast cancer. Patients were eligible if their cancer had not progressed after four to eight cycles of induction treatment with trastuzumab, pertuzumab, and a taxane. The study included patients with no brain metastases and patients with brain metastases without symptoms.
Patients were randomly assigned to receive:
- Tucatinib plus trastuzumab and pertuzumab.
- Placebo—a look-alike pill—plus trastuzumab and pertuzumab.
Doctors followed patients to measure progression-free survival, or how long they lived without their cancer growing or worsening, and to monitor side effects.
Key results patients should know
Patients who received tucatinib with trastuzumab and pertuzumab had a median progression-free survival of 24.9 months, compared with 16.3 months for those who received placebo with trastuzumab and pertuzumab—a difference of 8.6 months.
The tucatinib combination reduced the risk of cancer progression or death by approximately 36% compared with the placebo combination. The reported benefit was seen regardless of hormone receptor status and whether patients had a history of brain metastases.
Overall survival data—how long patients live—were not mature at the time of the progression-free survival analysis. Longer follow-up is needed to determine whether the combination also improves overall survival.
Side effects and safety
Common side effects reported with tucatinib in HER2CLIMB-05 included diarrhea, nausea, and increases in liver enzymes on blood tests. About 14% of patients stopped tucatinib because of side effects.
The FDA’s approval announcement notes that Tukysa’s prescribing information includes a boxed warning for hepatotoxicity, or liver injury. Other warnings and precautions address diarrhea, potential harm to an unborn baby, and increases in serum creatinine that do not affect kidney function. Patients should discuss side effects and monitoring with their oncology team.
What the approval means for patients
Tucatinib with trastuzumab and pertuzumab is now an FDA-approved maintenance option following induction treatment for adults with unresectable locally advanced or metastatic HER2-positive breast cancer. “Unresectable” means the cancer cannot be removed with surgery; “metastatic” means it has spread to other parts of the body.
Unlike Tukysa’s earlier approved breast cancer regimen, this maintenance combination does not include capecitabine chemotherapy. It is used after initial treatment rather than only after a prior HER2-directed regimen in the metastatic setting. Patients can discuss with their oncology team whether this maintenance approach is appropriate for their treatment plan.
About Tukysa
Tukysa is an oral medicine that targets HER2. Its FDA-approved breast cancer uses include:
- Maintenance treatment: In combination with trastuzumab and pertuzumab for adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.
- Previously treated advanced breast cancer: In combination with trastuzumab and capecitabine for adults with unresectable locally advanced or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least one prior anti-HER2-based regimen in the metastatic setting.
For the newly approved maintenance regimen, the recommended tucatinib dose is 300 mg by mouth twice daily with trastuzumab and pertuzumab, continued until the cancer progresses or side effects become unacceptable.
Reference
Dieras V, Curigliano G, Martin M, et al. HER2CLIMB-05: A Phase 3 Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as First-line Maintenance Therapy for HER2+ Metastatic Breast Cancer. J Clin Oncol. 2025 Dec 10:101200JCO2502600
