Entrectinib (Rozlytrek™) was approved by the U.S. Food and Drug Administration in August 2019 as the third tumor-agnostic cancer drug, meaning it targets a specific mutation of the cancer, not the organ of origin. The other two currently approved tumor-agnostic drugs are larotrectinib and pembrolizumab.
Entrectinib is a kinase inhibitor.
The drug is indicated for the treatment of adults with ROS1-positive, metastatic, non-small cell lung cancer. It’s also indicated for adult and pediatric patients 12 years old and older with metastatic or unresectable solid tumors that have a NTRK gene fusion without a known acquired resistance mutation that have progressed following treatment or have no alternative treatment options.
Administer 600 mg orally once daily. Dose reductions are recommended for certain adverse events (e.g., hematologic toxicity, cardiotoxicity, central nervous system [CNS] toxicity, hyperuricemia, hepatotoxicity). Discontinue permanently if adverse events persist after two dose reductions. Refer to the package insert for additional recommendations. Avoid concomitant use with strong or moderate CYP3A inhibitors; dose reduce if unavoidable.
Take orally with or without food but avoid grapefruit products. Make up a missed dose unless the next dose is within 12 hours.
The most common side effects are fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, vomiting, pyrexia, arthralgia, and vision disorders. Hematologic effects (e.g., anemia, lymphocytopenia, neutropenia) or cardiac effects (e.g., heart failure, QTc interval prolongation) have been reported. Approximately 25% of patients report CNS effects (e.g., cognitive impairment, mood disorders, dizziness, sleep disturbances), typically within three months of initiation. Skeletal fractures, vision changes, and hepatic toxicity have also been reported.
Assess patients’ NTRK gene fusion status or ROS1 rearrangement status prior to initiation. Monitor lab values, including complete blood count, electrolytes, liver function tests, and uric acid. Consider LVEF for patients with history or symptoms of heart failure. Assess QTc interval at baseline and periodically. Monitor for CNS adverse effects, tumor lysis syndrome, and hepatotoxicity. These or other clinically relevant adverse events may require holding the drug or dose reduction. Assess for concomitant drugs such as moderate and strong CYP3A inducers or drugs that prolong QT interval. Because of the potential for fetal harm, exclude pregnancy prior to initiation and ensure patients use ongoing effective contraception.
- Administer with or without food. Swallow the capsules whole and not crushed, chewed, or dissolved.
- Inform providers about all medications, including prescription, vitamins, and herbals.
- Avoid grapefruit products while taking entrectinib.
- Men should use contraception for at least three months after the final dose and women for at least five weeks following the final dose. Breastfeeding is not recommended and should be avoided for at least seven days after the last dose.
- Report signs or symptoms of congestive heart failure, CNS changes, bone fractures, hepatotoxicity, hyperuricemia, QT prolongation, or visual changes.
Clinical studies did not include sufficient numbers of older adults to determine whether they respond differently.
Because of the known embryo-fetal toxicity following exposure to entrectinib, nurses should use hazardous drug precautions when handling.
Patient Assistance Program
A financial assistance program is available at the manufacturer’s website.