FDA approved Tukysa (tucatinib) for HER2-Positive Breast and Colorectal CancersFDA approved Tukysa for Two Types of Advanced Cancer

Tukysa is a kinase inhibitor. The specific kinase targets are not described in the label.

Tukysa is indicated in combination with trastuzumab and capecitabine for adults with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. It is also indicated in combination with trastuzumab for adults with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. The colorectal cancer indication is approved under accelerated approval based on tumor response rate and durability of response; continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. For colorectal cancer, select patients based on HER2 overexpression or gene amplification and RAS wild-type status. FDA-approved tests for HER2 overexpression and gene amplification in colorectal cancer are not currently available; information on FDA-approved tests for RAS mutations is available at http://www.fda.gov/CompanionDiagnostics.

The recommended dosage of Tukysa is 300 mg orally twice daily with or without food, in combination with trastuzumab and capecitabine for breast cancer, or with trastuzumab for colorectal cancer, until disease progression or unacceptable toxicity. For patients with severe hepatic impairment, the recommended dosage is 200 mg orally twice daily. Advise patients to swallow tablets whole and not to chew, crush, or split. Do not ingest if broken, cracked, or not intact. Take approximately 12 hours apart and at the same time each day. If a dose is vomited or missed, take the next dose at its usual scheduled time. When given with Tukysa, the recommended capecitabine dosage is 1000 mg/m2 orally twice daily taken within 30 minutes after a meal; Tukysa and capecitabine can be taken at the same time. Refer to the Full Prescribing Information for trastuzumab and capecitabine for additional information. Dose reductions for adverse reactions: first reduction to 250 mg twice daily, second to 200 mg twice daily, third to 150 mg twice daily; permanently discontinue if unable to tolerate 150 mg twice daily. For diarrhea: Grade 3 without anti-diarrheal treatment, hold until recovery to ≤ Grade 1, then resume at same dose level; Grade 3 with anti-diarrheal treatment, hold until recovery to ≤ Grade 1, then resume at next lower dose level; Grade 4, permanently discontinue. For hepatotoxicity: Grade 2 bilirubin (>1.5 to 3 × ULN), hold until recovery to ≤ Grade 1, then resume at same dose level; Grade 3 ALT or AST (>5 to 20 × ULN) or Grade 3 bilirubin (>3 to 10 × ULN), hold until recovery to ≤ Grade 1, then resume at next lower dose level; Grade 4 ALT or AST (>20 × ULN) or Grade 4 bilirubin (>10 × ULN), permanently discontinue. Also, for ALT or AST >3 × ULN AND bilirubin >2 × ULN, permanently discontinue.

Trial data not available in label.

Warnings and precautions include diarrhea and hepatotoxicity. Dosage modifications for these adverse reactions are provided in the label. Contraindications are not reported in the label.

Tukysa provides a targeted treatment option for patients with HER2-positive metastatic breast cancer, including those with brain metastases, after prior anti-HER2 therapy. For colorectal cancer, it offers a combination regimen for RAS wild-type HER2-positive disease that has progressed after standard chemotherapy, under accelerated approval. Patient selection