FDA Approves Breast Cancer Treatment Through International Approval Pathway

The U.S. Food and Drug Administration (FDA) approved Tukysa™ (tucatinib) in combination with trastuzumab and capecitabine for the treatment of advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer that is unresectible or has spread to other parts of the body, including the brain, and who have received one or more prior treatments. This is the first new drug approved under Project Orbis, an international collaboration.

The FDA collaborated with the regulatory authorities of Australia, Canada, Singapore, and Switzerland for this review. The FDA was the only agency to approve tucatinib; the application is still under review at the other agencies.

The approval was based on the results of the phase III HER2CLIMB trial that included 612 patients with HER2+ advanced unresectable or metastatic breast cancer who had received prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine. About half of patients (48%) had brain metastases at the start of the trial.

All patients received trastuzumab and capecitabine plus either tucatinib or placebo.

Improved survival with the addition of tucatinib

Median progression-free survival (PFS; primary endpoint) among patients treated with tucatinib, trastuzumab, and capecitabine was 7.8 months compared with 5.6 months in those treated with placebo, trastuzumab, and capecitabine. Median overall survival in patients who received tucatinib, trastuzumab, and capecitabine was 21.9 months compared with 17.4 months in those who received placebo, trastuzumab, and capecitabine. The median PFS in patients with brain metastases at baseline who received tucatinib, trastuzumab, and capecitabine was 7.6 months compared with 5.4 months in patients who received placebo, trastuzumab, and capecitabine.

Common adverse events (AEs) associated with tucatinib are diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Tucatinib can cause serious AEs, including severe diarrhea associated with dehydration, acute kidney injury, and death. Patients should start anti-diarrheal medication as clinically indicated if diarrhea occurs. If patients experience severe diarrhea, the tucatinib dose should be interrupted or reduced. Tucatinib can also cause severe hepatotoxicity, and liver counts should be monitored every three weeks while patients are on treatment.