In HER2-positive breast cancer patients with brain metastases treated with trastuzumab and capecitabine, add-on tucatinib increased median overall survival from 12 months to 18.1 months in a phase 2 trial.
The results were presented as part of the American Society of Clinical Oncology virtual scientific program and published simultaneously in the Journal of Clinical Oncology.
At 1 year, 70% of the 198 patients who had been randomized to tucatinib were alive versus 47% of the 93 patients randomized to placebo. Tucatinib reduced the risk of death by 42% (P = .005).
“This is the first double-blind, randomized trial of systemic therapy to our knowledge [that demonstrated] clinically meaningful gains in [overall survival] among patients with [brain metastases], including those with active metastases,” Nancy Lin, MD, associate chief of the division of breast oncology at Dana-Farber Cancer Institute in Boston and colleagues wrote in the Journal of Clinical Oncology.
The findings come from a substudy of the HER2CLIMB trial, which had similar outcomes but didn’t separate women with brain metastases from others. The study won tucatinib’s maker, Seattle Genetics, Food and Drug Administration approval for tucatinib in combination with trastuzumab and capecitabine for patients with unresectable or metastatic HER2-postive disease after failure of at least one treatment for advanced disease. In the United States, tucatinib costs over $18,000 a month, according to GoodRX and other sources.
The newly approved indication for tucatinib includes patients with brain metastases, but Dr. Lin and colleagues drove the point home by analyzing HER2CLIMB data solely in the 291 subjects who had baseline CNS lesions, which occur in up to half of women with advanced HER2-positive breast cancer.
Amy Tiersten, MD, a professor at Mount Sinai Hospital in New York, was not involved in the study but is convinced of the clinical benefit of tucatinib. Tucatinib “will be the standard of care for all patients with brain metastases ... regardless of” previous treatments, she said.
“It’s a total game changer. The addition of tucatinib made a large difference, including a hefty impact on overall survival. It will be interesting to see if this drug will be useful in earlier stages to help prevent brain metastases,” Dr. Tiersten said.
Among the large benefits she alluded to, the median CNS progression-free survival (PFS) – free of lesion progression or death – was 9.9 months with tucatinib versus 4.2 months with placebo (P < .00001).
At 1 year, 40% of tucatinib patients, but no patients in the placebo arm, were alive and free of CNS progression. Tucatinib reduced the risk of intracranial progression or death by 68%.
Active vs. stable brain metastasis
Among the 117 patients who entered the trial with stable, treated brain metastases – most by radiation, the rest by surgery – the median CNS PFS was 13.9 months with tucatinib versus 5.6 months with placebo (P = .002). In this group, the median overall survival was 15.7 months in the tucatinib arm and 13.6 month in the placebo arm (P = .70).