FDA Approves Tukysa Combination as Maintenance for HER2-Positive Breast Cancer

The Food and Drug Administration (FDA) approved Tukysa (tucatinib) in combination with Herceptin (trastuzumab) and Perjeta (pertuzumab) on Oct. 7 as maintenance treatment for adults with HER2-positive breast cancer that is unresectable (cannot be removed with surgery) and locally advanced or metastatic (has spread to other parts of the body). Maintenance treatment is ongoing therapy given after a first round of treatment, known as induction, to help keep cancer from progressing.

The approval is based on results from the HER2CLIMB-05 trial, which enrolled 654 adults whose cancer had not worsened after induction treatment with Herceptin, Perjeta and a taxane (a type of chemotherapy).

What did the HER2CLIMB-05 trial show for Tukysa in HER2-positive breast cancer?

Patients who received Tukysa plus Herceptin and Perjeta lived a median of 24.9 months without their cancer worsening, compared with 16.3 months for patients who received placebo plus Herceptin and Perjeta. Progression-free survival, which measures how long patients live without their cancer growing or spreading, was the trial's primary end point and was assessed by the study investigators.

The results translated to a 36% lower risk of cancer progression or death with the Tukysa combination, and the difference between the two groups was unlikely to have come about by chance.

The trial also measured overall survival, or how long patients lived regardless of whether their cancer worsened. Those data were not yet mature at the time of the progression-free survival analysis, meaning more follow-up is needed before results can be reported.

Who was included in the HER2CLIMB-05 trial?

The randomized, double-blind, placebo-controlled trial included adults with HER2-positive breast cancer that was unresectable and locally advanced or metastatic. Patients with and without brain metastases (cancer that has spread to the brain) were eligible. In a double-blind trial, neither patients nor investigators know who is receiving the study drug and who is receiving placebo.

To enroll, patients needed to show no signs of cancer progression, as assessed by investigators, after four to eight cycles of induction treatment with Herceptin, Perjeta and a taxane.

Patients then took either 300 mg of Tukysa or placebo by mouth twice a day. Both groups also received Herceptin and Perjeta, given either intravenously (through a vein) or as Phesgo (pertuzumab, trastuzumab and hyaluronidase), a fixed-dose combination injected under the skin. Patients whose cancer was hormone receptor-positive could continue endocrine (hormone) therapy. Treatment continued until the cancer progressed or side effects became too severe to continue.

The FDA's recommended dosage of Tukysa is the same 300 mg twice a day in combination with Herceptin and Perjeta.

What side effects are linked to Tukysa maintenance treatment?

The prescribing information for Tukysa carries a boxed warning, the most serious type of warning on a drug label, for hepatotoxicity (liver damage).

The label also lists warnings and precautions for diarrhea, embryo-fetal toxicity (harm to a developing baby during pregnancy) and increased levels of serum creatinine, a waste product measured in blood tests to check kidney function. According to the FDA, the creatinine increase does not affect how the kidneys work.

What does this approval mean for patients?

For people with HER2-positive breast cancer whose disease has not progressed after initial treatment with Herceptin, Perjeta and a taxane, the FDA approval provides another option for continuing treatment and delaying cancer progression. In the HER2CLIMB-05 trial, adding Tukysa to Herceptin and Perjeta extended the time patients lived without their cancer worsening by more than eight months compared with Herceptin and Perjeta alone.

The treatment is intended as maintenance therapy, meaning patients begin Tukysa after completing their initial treatment and continue it as long as it is helping control the cancer and side effects remain manageable. Because the overall survival results are not yet mature, it is not yet known whether the combination helps patients live longer overall.

Patients should talk with their health care team about whether Tukysa is appropriate for them based on their previous treatments, cancer characteristics, overall health and potential side effects. Because Tukysa can cause serious liver problems and other side effects, patients may need regular monitoring during treatment.

References

1. "FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer." U.S. Food and Drug Administration. Posted: Oct. 7, 2026.

For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.