FDA Approves Tucatinib in Combination with Chemotherapy for HER2-Positive Breast Cancer


The FDA approved tucatinib in combination with chemotherapy for the treatment of adult patients with advanced forms of HER2-positive breast cancer.

The FDA approved tucatinib (Tukysa) in combination with chemotherapy (trastuzumab [Herceptin] and capecitabine [Xeloda]) for the treatment of adult patients with advanced forms of HER2-positive breast cancer that either cannot be removed with surgery or have spread to other parts of the body, including the brain, and who have received 1 or more prior treatments.

The FDA review of tucatinib was completed under Project Orbis in collaboration with the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (SMC, Switzerland). Though the FDA approved tucatinib, the application is still under review by 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,” said Richard Padzur, 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. “This approval represents an additional targeted treatment option for patients with HER2-positive breast cancer. 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.”

Approval of tucatinib was based on results from a clinical trial which enrolled 612 patients who had HER2-positive advanced unresectable or metastatic breast cancer and had prior treatment with trastuzumab, pertuzumab (Perjeta), and ado-trastuzumab emtansine (T-DM1; Kadcyla). Overall, 48% of enrolled patients had brain metastases at the start of the trial. 

Median progression-free survival (PFS), the trial’s primary endpoint, was 7.8 months with tucatinib, trastuzumab, and capecitabine, compared with 5.6 months in patients who received placebo, trastuzumab, and capecitabine.

Key secondary endpoints included overall survival (OS) and PFS in patients with brain metastases at baseline. The median OS in patients who received tucatinib, trastuzumab, and capecitabine was 21.9 months, compared with 17.4 months in those who were given placebo, trastuzumab, and capecitabine. Further, the median PFS in patients with brain metastases at baseline who were administered tucatinib, trastuzumab, and capecitabine was 7.6 months, compared to 5.4 months in participants who received placebo, trastuzumab, capecitabine. 

Common adverse events (AEs) observed in patients taking tucatinib were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Moreover, tucatinib can also cause serious AEs, including severe diarrhea associated with dehydration, acute kidney injury, and death. 

The FDA indicated that healthcare professionals should advise patients to notify their health care provider and begin antidiarrheals as clinically indicated should diarrhea occur. Additionally, if patients are experiencing severe diarrhea, the FDA recommended that tucatinib be interrupted or the dosage reduced. Tucatinib has also been known to cause severe hepatotoxicity, and the FDA suggests that healthcare professionals should monitor liver tests in patients taking tucatinib every 3 weeks while the patient is on treatment or as clinically indicated.

Women who are pregnant or breastfeeding have also been advised against taking tucatinib, as it may cause harm to a developing fetus or newborn baby. The FDA also advises healthcare professionals to instruct females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Tukysa and for at least one week after the last dose. Moreover, the FDA advises patients refer to the Full Prescribing Information of trastuzumab and capecitabine for information on pregnancy and contraception.

The FDA granted this application priority review and breakthrough therapy designation. Further, tucatinib was granted fast track designation and previously received orphan drug designation. 


FDA Approves First New Drug Under International Collaboration, A Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer [news release]. Published April 17, 2020. fda.gov/news-events/press-announcements/fda-approves-first-new-drug-under-international-collaboration-treatment-option-patients-her2. Accessed April 17, 2020. 

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