In updated analyses from the phase III HER2CLIMB trial reported in JAMA Oncology, Nancy U. Lin, MD, and colleagues found that the addition of tucatinib to trastuzumab and capecitabine showed improved outcomes among previously treated patients with HER2-positive breast cancer and baseline brain metastases and improved new brain lesion–free survival among all patients.
The trial supported the April 2020 approval of tucatinib in combination with trastuzumab and capecitabine for patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti–HER2-based regimens in the metastatic setting. Approval was based on findings of improved progression-free survival, overall survival, and objective response rate among all patients, and improved progression-free survival in those with brain metastases.
Study Details
In the double-blind trial, conducted between February 2016 and May 2019, 612 patients previously treated with trastuzumab, pertuzumab, and ado-trastuzumab emtansine were randomly assigned 2:1 to receive tucatinib (n = 410) or placebo (n = 202) in combination with trastuzumab and capecitabine. Brain metastases were present at baseline in 198 vs 93 patients.
This subgroup analysis found that tucatinib in combination with trastuzumab and capecitabine improved overall survival while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with HER2-positive metastatic breast cancer, including those with brain metastases.— Nancy U. Lin, MD, and colleagues
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Key Findings
Median follow-up was 29.6 months (range = 0.1–52.9 months), representing an additional 15.6 months of follow-up from the prior analysis.
Among patients with brain metastases at baseline, median overall survival was 21.6 months (95% confidence interval [CI] = 18.1–28.5 months) in the tucatinib group vs 12.5 months (95% CI = 11.2–16.9 months) in the control group (hazard ratio [HR] = 0.60, 95% CI = 0.44–0.81, P < .001). Estimated rates at 1 and 2 years were 70.0% vs 50.6% and 48.5% vs 25.1%.
Median central nervous system progression-free survival was 9.9 months (95% CI = 8.4–11.7 months) in the tucatinib group vs 4.2 months (95% CI = 3.6–5.7 months) in the control group (HR = 0.39, 95% CI = 0.27–0.56, P < .001). Estimated rates at 1 and 2 years were 38.4% vs 7.9% and 19.3% vs 0%.
Among 55 vs 20 patients with active brain metastases and measurable disease at baseline, intracranial objective response rates were 47.3% vs 20.0%, with a median duration of response of 8.8 vs 3.0 months.
Among all 612 patients, median new brain lesion–free survival was 24.9 months (95% CI = 17.8 months to not estimable) in the tucatinib group vs 13.8 months (95% CI = 9.6 months to not estimable) in the control group (HR = 0.55, 95% CI = 0.36–0.85, P = .006).
The investigators concluded, “This subgroup analysis found that tucatinib in combination with trastuzumab and capecitabine improved overall survival while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with HER2-positive metastatic breast cancer, including those with brain metastases.”
Dr. Lin, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Seagen Inc, in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit jamanetwork.com.
