FDA OKs New Drug for HER2-Positive Breast Cancer

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https://www.medpagetoday.com/hematologyoncology/br...

WASHINGTON -- The FDA approved tucatinib (Tukysa) on Friday for treating advanced, HER2-positive breast cancer patients who have received at least one prior therapy.

Approved in combination with trastuzumab (Herceptin) plus capecitabine, the highly selective HER2-directed tyrosine kinase inhibitor is indicated for patients with metastatic breast cancer or advanced but unresectable disease.

Supporting the approval were data from the HER2CLIMB study, which randomized 612 previously treated breast cancer patients 2:1 to trastuzumab and capecitabine plus either tucatinib or placebo.

Median progression-free survival (PFS), the study's primary endpoint, was 7.8 months in the tucatinib arm compared with 5.6 months in the placebo arm (HR 0.54, 95% CI 0.42-0.71, P<0.001), and PFS at 1 year was 33.1% versus 12.3%, respectively.

Median overall survival was also improved in the tucatinib arm, at 21.9 months compared with 17.4 months for those on placebo (HR 0.66, 95% CI 0.50-0.87, P=0.0048), with more patients on tucatinib alive at 2 years (44.9% vs 26.6% with placebo).

Objective responses were nearly twice as frequent in the tucatinib combination arm (40.6% vs 22.8%).

"With highly significant and clinically important results for overall and progression-free survival, the addition of Tukysa 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," investigator Eric Winer, MD, of Dana-Farber Cancer Institute in Boston, said in a statement from manufacturer Seattle Genetics.

Prior anti-HER2 therapies among patients in HER2CLIMB included trastuzumab, pertuzumab (Perjeta), and ado-trastuzumab emtansine (Kadcyla), or some combination of these drugs.

"The clinical trial supporting this approval enrolled and specifically studied patients with active brain metastases in addition to the overall population enrolled, which also demonstrated benefit in this subgroup," said Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases, in an agency statement.

Results among this subgroup, which made up 48% of the patients, were consistent with the overall population, with a median PFS of 7.6 months versus 5.4 months for the tucatinib and placebo arms, respectively (HR 0.48, 95% CI 0.34-0.69, P<0.00001). Overall survival was likewise improved (HR 0.58, 95% CI 0.40-0.85).

In FDA's announcement, they noted a host of adverse events with tucatinib, the most common of which were abdominal pain, anemia, decreased appetite, diarrhea, fatigue, headache, hepatotoxicity, nausea and vomiting, palmar-plantar erythrodysesthesia, rash, and stomatitis. They also warned on the risk of acute kidney injury, hepatotoxicity, severe diarrhea, and death with the drug.

Of note, tucatinib was reviewed and approved under Project Orbis, which "provides a framework for concurrent submission and review of oncology drug applications among the FDA's international collaborators," explained Pazdur.

The tucatinib submission marks the first in partnership with Singapore and Switzerland and this and past collaborations have included Australia and Canada.