April 17, 2020
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FDA approves Tukysa as part of combination therapy for breast cancer

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Richard Pazdur, MD
Richard Pazdur

The FDA approved tucatinib in combination with chemotherapy for the treatment of certain adults with previously treated advanced HER2-positive breast cancer.

The approval applies to use of tucatinib (Tukysa, Seattle Genetics) with trastuzumab (Herceptin, Genentech) and capecitabine for patients whose cancer can’t be removed with surgery or has spread to other parts of the body, and who received at least one prior anti-HER2-based regimen in the metastatic setting.

Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR.

The FDA approved the agent based on results of the randomized phase 3 HER2CLIMB trial, which included 612 patients with HER2-positive advanced unresectable or metastatic breast cancer.

All patients received prior treatment with trastuzumab, pertuzumab (Perjeta, Genentech) and ado-trastuzumab emtansine (Kadcyla, Genentech), and nearly half (48%) of patients had brain metastases at the start of the trial.

Researchers randomly assigned patients 2:1 to tucatinib 300 mg or placebo twice daily in combination with trastuzumab — dosed at 6 mg/kg once every 21 days, with a loading dose of 8 mg/kg on day 1 of the first cycle — and capecitabine, dosed at 1,000 mg/m² twice daily on days 1 to 14 of each 21-day cycle.

PFS served as the primary endpoint. OS and PFS among patients with brain metastases at baseline served as key secondary endpoints.

As Healio previously reported, results showed longer median PFS (7.8 months vs. 5.6 months) and OS (21.9 months vs. 17.4 months) in the tucatinib group.

Researchers also reported longer median PFS with tucatinib among patients with brain metastases at baseline (7.6 months vs. 5.4 months).

The most common adverse events among tucatinib-treated patients included diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia and rash.

The FDA collaborated on this review with the Australian Therapeutic Goods Administration, Health Canada, Health Sciences Authority in Singapore and Swissmedic in Switzerland as part of an international collaboration known as Project Orbis.

The application remains under review by the other agencies.

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release. “We are pleased to work with our Singapore and Switzerland colleagues for the first time, and to continue working alongside our Australian and Canadian colleagues as we facilitate new treatment options for patients — like today's first new molecular entity under Project Orbis.”

The FDA previously granted priority review and breakthrough therapy designation to tucatinib for this indication.