In April 2020, the FDA approved the use of a new tyrosine kinase inhibitor, Tukysa (tucatinib), in combination with Herceptin (trastuzumab) and Xeloda (capecitabine), for the treatment of adults with advanced unresectable (cannot be removed by surgery) or metastatic (spreading to other organs) HER2-positive breast cancer, including patients with brain metastases, who have received 1 or more previous therapies for metastatic disease.
At the 2021 ASCO Annual Meeting, Giuseppe Curigliano, MD, PhD, Associate Professor of Medical Oncology at the University of Milano, Italy, and lead study investigator, presented updated results from the HER2CLIMB clinical trial.
This study compared the use of tucatinib plus trastuzumab and capecitabine (tucatinib group) versus placebo plus trastuzumab and capecitabine (placebo group) in patients with HER2-positive metastatic breast cancer.
The long-term results demonstrated an average of 5.5-month improvement in survival in the tucatinib group compared with the placebo group after an additional 15.6 months of follow-up. A benefit was also seen in the time without disease progression. These benefits were observed across all subgroups of patients, including patients with or without brain metastases.
“Late-stage HER2-positive metastatic cancer has proved difficult to treat,” Dr. Curigliano said. “These data further support that treatment with the tucatinib regimen helps patients live longer compared to trastuzumab and capecitabine alone.”
The HER2CLIMB Study
The original HER2CLIMB study randomly assigned patients to tucatinib versus placebo, each in combination with trastuzumab and capecitabine. All patients had locally advanced or metastatic HER2-positive breast cancer after their disease progressed during previous treatments. The study enrolled patients with and without brain metastases at baseline, including those with active brain metastases.
The use of tucatinib in combination with trastuzumab and capecitabine reduced the risk of death by 34% in the total study population, and in patients with brain metastases, the risk for disease progression or death was reduced by 52%.
Based on these data, the study protocol was amended to allow patients to cross over from the placebo arm to the tucatinib arm.
Updated Results Confirm Survival Benefit
At the ASCO meeting, Dr. Curigliano presented updated results from the HER2CLIMB study that included long-term overall survival, time without disease progression, and safety in the total study population, after about 2 years from the time the last patient entered the study.
At the time of data cutoff, 35 patients in the tucatinib group and 1 patient in the placebo group were still receiving their study treatment. In total, 26 patients crossed over from the placebo group to the tucatinib group, and 9 of these patients continued to receive tucatinib.
For this updated analysis, the average duration of follow-up was almost 3 years (29.6 months). The average overall survival in the tucatinib group was 24.7 months versus 19.2 months in the placebo group.
“The data demonstrated that the overall survival benefit with tucatinib was maintained with an additional 15.6 months of follow-up,” said Dr. Curigliano. He added that the benefit was consistent across all prespecified patient subgroups.
“Overall, there was a 27% reduction in the risk of death for patients in the tucatinib arm compared with the placebo arm,” Dr. Curigliano added.
The increased time without disease progression with the tucatinib regimen was also maintained at a longer follow-up. There was a 43% reduction in the risk of cancer progression in the tucatinib arm, for an average time without disease progression of 7.6 months with tucatinib versus 4.9 months with placebo.
Consistent with the primary analysis, in this updated analysis, the tucatinib regimen continued to be safe and well-tolerated with the longer follow-up.
“In the 15.6 months since the primary analysis, only 1 additional patient discontinued tucatinib due to an adverse event,” Dr. Curigliano said.
The most common side effects in patients who received tucatinib were diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Serious (grade 3 or 4) side effects remained stable with the additional follow-up.
- Long-term results demonstrated an average of 5.5-month improvement in survival in the tucatinib group versus the placebo group after an additional 15.6 months of follow-up
- The use of tucatinib in combination with trastuzumab and capecitabine reduced the risk of death by 34% in the total study population
- Tucatinib also reduced the risk of disease progression or death by 52% in patients with brain metastases
- The average overall survival in the tucatinib group was 24.7 months versus 19.2 months in the placebo group
- The most common side effects in patients who received tucatinib were diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting