On Apr. 17, 2020, as part of Project Orbis, the U.S. Food and Drug Administration (FDA) approved Seagen’s Tukysa (tucatinib) in combination with chemotherapy (trastuzumab and capecitabine) for the treatment of adult patients with advanced forms of HER2-positive breast cancer that can’t be removed with surgery, or has spread to other parts of the body, including the brain, and who have received one or more prior treatments.

The FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (SMC, Switzerland) on this review. This is the first Project Orbis partnership between the FDA, HSA and Swissmedic. Efficacy was demonstrated in the HER2CLIMB trial (NCT02614794) enrolling 612 patients with HER2-positive metastatic breast cancer who had prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine.

Tukysa is a kinase inhibitor meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. Tukysa is approved for treatment after patients have taken one or more anti-HER2-based regimens in the metastatic setting. The FDA approved Tukysa based on the results of a clinical trial enrolling 612 patients who had HER2-positive advanced unresectable or metastatic breast cancer and had prior treatment with trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients with previously treated and stable brain metastases, as well as those with previously treated and growing or untreated brain metastases, were eligible for the clinical trial, and 48% of enrolled patients had brain metastases at the start of the trial.

The primary endpoint was progression-free survival (PFS), or the amount of time when there was no growth of the tumor. The median PFS in patients who received Tukysa, trastuzumab, and capecitabine was 7.8 months compared to 5.6 months in those patients who received placebo, trastuzumab, and capecitabine. Overall survival and PFS in patients with brain metastases at baseline were key secondary endpoints. The median overall survival in patients who received Tukysa, trastuzumab, and capecitabine was 21.9 months compared to 17.4 months in patients who received placebo, trastuzumab, and capecitabine. The median PFS in patients with brain metastases at baseline who received Tukysa, trastuzumab and capecitabine was 7.6 months compared to 5.4 months in patients who received placebo, trastuzumab and capecitabine.

Common side effects for patients taking Tukysa were diarrhea, palmar-plantar erythrodysesthesia (burning or tingling discomfort in the hands and feet), nausea, fatigue, hepatotoxicity (liver damage), vomiting, stomatitis (inflammation of the mouth and lips), decreased appetite, abdominal pain, headache, anemia and rash.

Tukysa can cause serious side effects including severe diarrhea associated with dehydration, acute kidney injury and death. Health care professionals should advise patients to notify their health care provider and start antidiarrheals as clinically indicated if diarrhea occurs. If patients are experiencing severe diarrhea, Tukysa should be interrupted or the dosage reduced. Tukysa can also cause severe hepatotoxicity. Health care professionals should monitor liver tests in patients taking Tukysa every three weeks while the patient is on treatment or as clinically indicated.

Women who are pregnant or breastfeeding should not take Tukysa because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to tell 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.