New data from HER2CLIMB shows tucatinib prevents progression of brain metastases

Targeted treatment for metastatic, HER2-positive breast cancer shows benefits for people with brain mets
ASCO 2020
May 29, 2020
By: 
Eric Fitzsimmons, Copy Editor and Content Coordinator

A new analysis of the HER2CLIMB trial, presented May 29 as part of the 2020 ASCO Annual Meeting, looks further into the benefits that adding tucatinib (Tukysa) has on treating brain metastases in people with stageinfo-icon IV HER2-positive breast cancer. The new data shows adding tucatinib to treatment prevents brain metastases from growing. They also show tucatinib has an effect whether the brain metastases are stable, progressing, or have never been treated.

Notably, people with brain mets who received tucatinib lived longer overall than those who received standard treatment without tucatinib.

Background

Results from the HER2CLIMB trial were first presented at the San Antonio Breast Cancer Symposium in December 2019 and led the Food and Drug Administration to approve tucatinib in April 2020. People in the trial had metastaticinfo-icon HER2-positive breast cancer that had grown despite treatment with HER2-targeted therapies, specifically trastuzumabinfo-icon (Herceptininfo-icon), pertuzumabinfo-icon (Perjeta), and ado-trastuzumab emtansine (Kadcyla). The study found participants given tucatinib, trastuzumab, and the oralinfo-icon chemotherapyinfo-icon capecitabineinfo-icon (Xelodainfo-icon) went longer without cancer progressing and lived longer compared to a control groupinfo-icon of participants given a placeboinfo-icon with trastuzumab and capecitabine.

The HER2CLIMB trial included people with brain metastases. This group is often excluded from studies because the blood-brain barrierinfo-icon, which is meant to protect our central nervous systeminfo-icon from outside substances, blocks many medicines from reaching tumors in the brain. Tucatinib is a small-molecule tyrosine kinase inhibitor. Because of the small size of its molecules, researchers were interested in its ability to get through the blood-brain barrier and treat metastases in the brain.

Results presented in December included people with and without brain metastases. In a secondary goal of the trial that looked only at people with brain metastases, researchers found participants went longer without cancer growing when given tucatinib. The new analysis presented at ASCO looked specifically at those with brain mets to better understand the effect of tucatinib on that conditioninfo-icon.

Results

The study included 291 participants who had breast cancer metastases in the brain when joining the study. Of these, 117 had brain mets that had been treated and were stable. There were also 66 people with brain metastases that had never been treated and 108 whose brain metastases progressed during their last treatment.

The study found that people in the tucatinib group went longer without cancer in the brain or central nervous system growing, no matter how or whether their brain mets had been treated before.

One year after starting the trial, 40.2 percent of people in the tucatinib group had no cancer progressioninfo-icon in the brain. But everyone in the control group had cancer progression there.

This was reflected in the average time people went without progression in the brain:

  • 9.9 months for people given tucatinib
  • 4.2 months for people in the control group

These HER2CLIMB results showed that people with brain mets given tucatinib with trastuzumab and capecitabine lived longer than people given a placebo with trastuzumab and capecitabine. On average:

  • People given tucatinib lived 18.1 months.
  • People in the control group lived 12.0 months.

In patients who had brain tumors that could be measured, researchers noted:

  • 47 percent of people given tucatinib had tumors that responded to treatment.
  • 20 percent of people in the control group had tumors that responded to treatment.

The ASCO analysis further broke down the results into people who had stable brain metastases and people who had active brain metastases, meaning they were untreated or had grown despite treatments. In both groups, people who got tucatinib went longer without cancer growing in the brain.

Researchers also looked at continued treatment when progression happened only in the brain during the study. Those people received local therapyinfo-icon, then remained on their assigned treatment. People given tucatinib went longer between that first progression and cancer growing in the brain again. They also went longer from starting the trial to a second progression:

  • People given tucatinib went 15.9 months.
  • People in the control group went 9.7 months.

Side effects were not discussed in this analysis, but the original results showed 80.9 percent of all participants given tucatinib had diarrhea, and 63.4 percent reported hand-foot syndrome. Side effects led 5.7 percent of people to stop tucatinib, compared to 3.0 percent of people in the control group.

What this means for you

The researchers say that brain metastases occur in about half of people diagnosed with HER2-positive metastatic breast cancer. We often don’t know how treatments will work on brain metastases because people who have them are excluded from clinicalinfo-icon trials, but we do know the blood-brain barrier makes it hard for medicines to reach cancer in the brain.

HER2CLIMB showed that people with breast cancer metastases in the brain went longer without cancer growing anywhere. This new analysis expands what we know about tucatinib’s effect on brain metastases, showing that it prevents the progression of metastases in the brain specifically, and that even after one progression on the medicineinfo-icon, tucatinib could still have an effect alongside local treatment.

For people with HER2-postitive metastatic breast cancer who have or are concerned about brain mets, tucatinib and HER2CLIMB are important findings for a diagnosisinfo-icon that is both difficult to treat and overlooked in research. Tucatinib provides a new treatment option that is backed up by strong data on brain metastases. The design of the trial and analyses of the findings also show it’s possible for future researchers to study the impact of full-body therapies on breast cancers that travel to the brain.

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Additional Related Topics 
Metastatic
Targeted Therapy