The new cancer drug Tukysa (tucatinib), when given in combination with Herceptin (trastuzumab) and capecitabine, dramatically improved outcomes for patients with HER2-positive advanced breast cancer that has spread to the brain, according to data presented by Nancy U. Lin, MD, Associate Chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, MA, at the 2020 ASCO annual meeting.
Tucatinib is a member of the tyrosine kinase inhibitor drug class and is currently approved only for the treatment of patients with HER2-positive breast cancer. Tucatinib is the first tyrosine kinase inhibitor to show an improvement in overall survival in patients with this type of breast cancer.
In April 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of adults with advanced HER2-positive breast cancer that cannot be removed by surgery or that has spread (metastasized) to other parts of the body—including the brain—and who have received at least 1 other anti-HER2 treatment. This approval was based on the results of the phase 3 HER2CLIMB clinical trial.
Clinical trials are designed to test the safety and effectiveness of new drugs, and phase 3 clinical trials, such as this, are typically the last step before the FDA’s approval of a drug.
Although anti-HER2 therapies have improved survival in patients with HER2-positive breast cancer, about half of the patients with HER2-positive advanced breast cancer will eventually have brain metastases, meaning their cancer will spread to the brain. Unfortunately, these patients do not typically have as many treatment options as patients whose cancer has not spread to the brain. According to Dr. Lin, more effective and tolerable treatment options are desperately needed for these patients. Therefore, the approval of tucatinib provides an important new treatment option for these patients.
The HER2CLIMB Study
In the HER2CLIMB clinical trial, 612 patients who had already received treatment with trastuzumab, Perjeta (pertuzumab), and Kadcyla (ado-trastuzumab emtansine) were randomly assigned to 1 of 2 groups. One group of 410 patients received tucatinib by mouth twice daily, given in combination with trastuzumab and capecitabine. A smaller group of 202 patients were given placebo along with trastuzumab and capecitabine.
The investigators previously published the first results from the study, which showed that patients who received tucatinib lived longer, and lived longer without the cancer progressing further. These promising survival results applied to all patients, including those who had or did not have brain metastases.
At the ASCO meeting, Dr. Lin focused more specifically on the 291 patients who had brain metastases when they joined the clinical trial.
“At 1 year, 40% of patients randomized to tucatinib versus 0% of patients randomized to placebo were alive and free of central nervous system progression,” reported Dr. Lin. “And at 1 year, 70% of patients randomized to tucatinib were alive versus 47% of patients randomized to placebo,” she noted.
Increased Progression-Free Survival
One of the most important measurements in the study was the time without the cancer progressing to the brain (what scientists call central nervous system progression). This told the researchers the length of time from each patient’s enrollment in the study to the point that the cancer progressed to the brain, or until death.
The average time without disease progression to the brain was 9.9 months in patients who received tucatinib versus 4.2 months in the patients who received placebo. “This is an improvement of greater than 5 months,” Dr. Lin said.
Among the patients who had active brain metastases—meaning they had received treatment for the brain metastases and were getting worse, or they had not been treated for them and the cancer was progressing—40% of patients who received tucatinib were alive and 40% of them were free of central nervous system progression at 1 year. By contrast, none of the patients who received placebo were still alive by 1 year.
“These central nervous system progression-free survival results represent a statistically significant and clinically meaningful delay in progression in the brain,” she said.
The average overall survival, or the length of time from the start of treatment that half of the patients in the study were still alive, was 18.1 months with tucatinib compared with 12 months in the patients who did not receive tucatinib, which is an improvement of more than 6 months.
In patients with brain metastases that were becoming worse, the average overall survival was 11.6 months in the placebo group compared with 20.7 months in the tucatinib group, which was a more than 9-month improvement in the average of survival for patients whose cancer had spread to the brain and was progressing.
Based on these findings, the investigators stated that “the addition of tucatinib to trastuzumab and capecitabine reduced the risk of central nervous system progression or death by two-thirds.”
- At 1 year, 40% of patients who received tucatinib were alive and free of brain metastasis progression versus none of the patients who received placebo
- In patients with a brain metastasis that was still progressing, the average overall survival was extended from 11.6 months with placebo to 20.7 months with tucatinib
- Overall, the addition of tucatinib to trastuzumab and capecitabine reduced the risk of brain metastasis progression or death by two-thirds