NEW YORK – The US Food and Drug Administration today approved tucatinib (Seattle Genetics' Tukysa) in combination with trastuzumab (Genentech's Herceptin) and capecitabine for adults with advanced unresectable or metastatic HER2-positive breast cancer, including those who have experienced brain metastases.
Tucatinib, which received priority review and breakthrough therapy designation from the FDA, was approved based on data from the HER2CLIMB trial, a randomized evaluation of more than 600 advanced, HER2-positive breast cancer patients. In that study, 48 percent had brain metastases. The primary endpoint was progression-free survival, which was evaluated by blinded independent reviewers for the first 480 randomized patients.
Among patients who received the tucatinib-containing regimen, the median PFS was 7.8 months versus 5.6 months in those receiving just trastuzumab and capecitabine. The median PFS in those whose cancers had spread to the brain was 7.6 months versus 5.4 months, in the tucantinib and comparator arm, respectively.
Median overall survival in the trial was 21.9 months for those receiving tucatinib, trastuzumab, and capecitabine compared to 17.4 months for those receiving just trastuzumab and capecitabine.
"With highly significant and clinically important results for overall and progression-free survival, the addition of [tucatinib] to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting," said Eric Winer, chief of the division of breast oncology at Dana-Farber Cancer Institute and senior author of HER2CLIMB. He highlighted that the approval is particularly meaningful given its activity in patients with brain metastasis, since up to half of breast cancer patients see their cancers spread to the brain.
In a note to investors, William Blair analyst Andy Hsieh wrote that the second-line indication for tucatinib is broader than the indication Seattle Genetics had outlined in its new drug application. "It is our view that … Tukysa [has] mega-blockbuster potential, given the vast improvement and differentiation relative to standard of care," Hsieh wrote.
Patients treated with tucatinib commonly experienced diarrhea, burning discomfort in the hands and feet, nausea, fatigue, and liver damage. In the HER2CLIMB study, 26 percent receiving tucatinib experienced serious adverse reactions. The FDA noted in approving the drug that tucatinib can cause severe diarrhea, which can lead to dehydration, kidney injury, and death, and patients experiencing severe diarrhea may need dose reductions. The risk of liver toxicity may necessitate monitoring using liver tests.
In approving the drug, Richard Pazdur, director of the FDA’s Oncology Center of Excellence, highlighted that tucatinib was approved four months ahead of the expected approval date for the drug, which demonstrates that the agency is working hard to ensure that the pandemic isn't negatively impacting patients' access to novel cancer drugs. "We recognize that patients with cancer constitute a vulnerable population at risk of contracting the coronavirus disease," Pazdur said in a statement. "In this critical time, we remain steadfast in our commitment to patients with cancer and doing everything we can to expedite oncology product development."