The Food and Drug Administration (FDA) has approved Tukysa (tucatinib; Seattle Genetics), in combination with trastuzumab and capecitabine, for treatment of adult patients with advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, including patients with brain metastases, who have received 1 or more prior anti-HER2-based regimens in the metastatic setting.

The approval of tucatinib, a tyrosine kinase inhibitor of HER2, was based on data from the HER2CLIMB study that included 612 patients with HER2-positive, unresectable locally advanced or metastatic breast cancer, with or without brain metastases, and prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine separately or in combination, in the neoadjuvant, adjuvant or metastatic setting. Patients were randomized to receive tucatinib or placebo in combination with trastuzumab and capecitabine. The primary end point of the study was progression-free survival (PFS); key secondary end points included overall survival and PFS in patients with brain metastases at baseline.

Findings from the first 480 study participants showed a median PFS of 7.8 months among patients treated with tucatinib (n=320) compared with 5.6 months among those who received placebo (n=160) (hazard ratio [HR] 0.54 [95% CI, 0.42-0.71; P <.00001); median PFS in patients with brain metastases at baseline was 7.6 months with tucatinib compared with 5.4 months with placebo (HR 0.48 [95% CI 0.34-0.69]; P <.00001). Median overall survival in patients who received tucatinib was 21.9 months vs 17.4 months in the placebo group (HR 0.66 [95% CI, 0.50-0.87]; P =.00480).

As for safety, the most common adverse reactions included diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. In the study, 81% of patients who received tucatinib experienced diarrhea; median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. 


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Commenting on the approval, 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: “We recognize that patients with cancer constitute a vulnerable population at risk of contracting the coronavirus disease. Tukysa was approved 4 months prior to the FDA goal date, providing an example of this commitment and showing how our regular work in reviewing treatments for patients with cancer is moving forward without delay.”

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Tukysa is supplied as 50mg and 150mg tablets. Seattle Genetics has designated Biologics by McKesson and Onco360 as the specialty pharmacy providers for the product. 

For more information visit seattlegenetics.com.