News > Tucatinib plus T-DM1 effective against HER2-positive breast cancer | SABCS 2023

Tucatinib plus T-DM1 effective against HER2-positive breast cancer | SABCS 2023

Study results offer new option for people with locally advanced or metastatic HER2-positive breast cancer that has spread to the brain

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Tucatinib is a tyrosine kinase inhibitor (TKI) drug used to treat metastatic HER2-positive breast cancer in combination with trastuzumab and capecitabine. The Food and Drug Administration approved the drug combination in 2020 based on results of the HER2CLIMB clinical trial. The trial and approval were noteworthy because they included people with brain metastases, a group often excluded from cancer clinical trials.

About 15% to 20% of all women diagnosed with metastatic breast cancer have brain metastasis. Local treatments—such as radiation therapy—are sometimes the only option. Most drug therapies do not work because they are not able to cross the blood-brain barrier designed to protect the brain from harm. As a small-molecule targeted therapy, tucatinib is able to cross this barrier to reach cancer cells in the central nervous system. This new study looks at tucatinib in combination with trastuzumab emtansine (T-DM1) for previously treated, locally advanced or metastatic HER2-positive breast cancer.


Tucatinib given in combination with trastuzumab emtansine is effective as a second-line treatment for locally advanced or metastatic HER2-positive breast cancer, according to results of the HER2CLIMB-02 phase III, randomized, double-blind clinical trial. Cancer growth was measured using RECIST 1.1, a standard used by doctors to determine whether new drugs are working, with these key results:

  • T-DM1 and tucatinib and outperformed T-DM1 plus placebo (9.5 months versus 7.4 months without cancer progression).
  • People taking tucatinib had a 24% lower risk of cancer progression or death.
  • The data for people with brain metastases show a positive trend in favor of tucatinib.
  • Results were consistent across subgroups (e.g., prior treatment, HR status, region).

In general, the drug combination was well tolerated. The most common side effects were nausea, diarrhea, and fatigue. Around 16% of people taking tucatinib reported moderate to severe alanine and aspartate aminotransferase elevations, signs of liver damage.

The study population included 468 people with locally advanced or metastatic HER2-positive breast cancer in North America, Europe/Israel, and the Asia-Pacific. More than half had HR-positive disease. Around half had brain metastases currently or at some point. Nearly one-quarter of both the study group and the control group had active brain metastases at the time of study. All had prior treatment with trastuzumab and chemotherapy for either early-stage or metastatic disease. The study was not open to people who had been treated with trastuzumab deruxtecan (T-DXd or Enhertu).

What does this mean for you?

If you have HER2-positive breast cancer, you may have a new treatment option. Tucatinib is already approved for locally advanced or metastatic HER2-positive breast cancer in combination with capecitabine and trastuzumab. The new trial demonstrates that it is also effective as a second treatment when combined with trastuzumab emtansine.

The results left some unanswered questions regarding when and how to best fit the new drug combination into a treatment plan. The study author suggests that it would be best used as a second treatment, most likely as an alternative to the combination of tucatinib/trastuzumab/capecitabine for cancers with brain metastases. Trastuzumab deruxtecan is still preferred as the second treatment for cancers that have not spread to the brain.

If you are choosing among these treatments, ask about side effects. The two combinations with tucatinib can cause different side effects. While both bring the risk of nausea and diarrhea, the three-drug combination is associated with hand-foot syndrome, while tucatinib/T-DM1 brings some risk of liver damage.


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