Written by: Katie Carter, PharmD, BCPS, IU Simon Cancer Center
Description: The purpose of this PQI is to highlight tucatinib and its usage and management in advanced unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens in the metastatic setting.
Background: Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2, a growth factor receptor over-expressed in various types of cancers.1 Tucatinib binds to the HER2 protein, inhibiting its role in signaling pathways and ultimately the growth of HER2-expressing cells.
Tucatinib, in combination with trastuzumab and capecitabine, is being studied in the HER2CLIMB trial that enrolled patients with locally advanced unresectable or metastatic HER2 positive breast cancer who had previously been treated with trastuzumab, pertuzumab, or trastuzumab emtansine. Patients received either tucatinib 300 mg orally twice daily or placebo in addition to trastuzumab and capecitabine.2
|Tucatinib Group||Placebo Group|
|PFS at 1 year||33.1%||12.3%|
|Median PFS duration||7.8 months||5.6 months|
|OS at 2 years||44.9%||26.6%|
|Median OS duration||21.9 months||17.4 months|
Additionally, researchers analyzed the subgroup of patients with brain metastases and found significantly increased PFS with tucatinib in this patient population as well, reporting primary results of PFS at one year of 24.9% in the tucatinib group compared to 0% in the placebo group. Presented at the 2020 ASCO Annual Meeting, an exploratory analysis in the HER2CLIMB trial of intracranial efficacy in patients with brain metastases who received tucatinib combination versus placebo group: a 42% reduction in the risk of death, a 68% reduction in the risk of CNS disease progression or death, and an increase in intracranial response rate (47% vs. 20%) for patients who had active measurable intracranial lesions at baseline.5
PQI Process: Identify eligible HER2 positive patients as potential candidates for tucatinib. Upon receiving a prescription for tucatinib:
- Verify appropriate starting dose: typically 300 mg by mouth two times daily
- Confirm orders for capecitabine and trastuzumab
- Drug interactions: avoid concomitant strong CYP3A4 and CYP2C8 inhibitors and inducers
- When to adjust which agent:
- All side effects should be assessed for relationship to tucatinib, capecitabine, and/or trastuzumab
- Liver function abnormalities: tucatinib dose should be adjusted
- Left ventricular ejection fraction (LVEF): tucatinib should be held if > 16% reduction from baseline, LVEF below limits of normal and > 10% reduction from baseline, or LVEF < 40%
- QTc prolongation: tucatinib dose should be adjusted, regardless of relationship to drug
|Dose Reduction||Recommended Dose||How to Supply|
|1st dose reduction||250 mg PO BID||One 150 mg tablet + two 50 mg tablets BID|
|2nd dose reduction||200 mg PO BID||One 150 mg tablet + one 50 mg tablet BID|
|3rd dose reduction||150 mg PO BID||One 150 mg tablet BID|
Patient Centered Activities:
- Provide Oncology Chemotherapy Education (OCE) sheet
- Provide Tucatinib Patient Guided Resource
- Administration: can be taken with or without food at the same time twice each day and at the same time as the capecitabine in the regimen
- Counsel patient on common side effects
- Diarrhea (80.9%)
- Provide Oral Chemotherapy Education Supplemental Sheet
- Reported to be manageable with short courses of antidiarrheals
- Recommend antidiarrheal agents to have on hand when starting tucatinib
- Palmar-plantar erythrodysaesthesia syndrome (63.4%)
- Nausea (58%), vomiting (35.9%)
- Fatigue (45%)
- Increased liver transaminases (20%)
- Reported to be transient and reversible
- Stomatitis, headache, decreased appetite also reported
- Diarrhea (80.9%)
- Storage: store at room temperature in the original bottle; do not remove desiccant from bottle. Once the bottle is opened, medication should be used within 3 months
- Financial Assistance:
- Can call 4SECURE or visit SeaGenSecure.com
- Patient Assistance Program, Claims Appeal and Patient Assistance, and Commercial Out-of-Pocket Assistance are available
- English DP, Rogue DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Mol Diagn Ther. 2013;17(2):85-99.
- Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. NEJM. 2020; 382:597-609.
- Seattle Genetics. Available at https://www.seagen.com/science/pipeline/tucatinib.
- Tucatinib combination extends survival in HER2- positive metastatic breast cancer, including patients with brain metastases. The ASCO Post. Available at: https://www.ascopost.com/issues/january-25-2020/tucatinib-combination-extends-survival-in-her2-positive-metastatic-breast-cancer/. Published JAN 25, 2020.
- Lin NU, Borges V, Anders C, et al. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. JCO. 2020, JCO2000775. doi: 10.1200/JCO.20.00775.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.