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Authors

  1. Aschenbrenner, Diane S. MS, RN

Abstract

* Entrectinib (Rozlytrek) has been approved by the Food and Drug Administration to treat adolescent and adult patients whose solid tumor cancers are related to a specific genetic defect known as neurotrophic tyrosine receptor kinase gene fusion, and for whom there are no effective treatments.

 

* Several warnings and precautions are listed on entrectinib's labeling, including congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT interval prolongation, vision disorders, and embryo-fetal toxicity.

 

 

Article Content

Entrectinib (Rozlytrek) has been approved by the Food and Drug Administration (FDA) to treat adolescent and adult patients whose solid tumor cancers are related to a specific genetic defect known as neurotrophic tyrosine receptor kinase (NTRK) gene fusion, and for whom there are no effective treatments. Entrectinib is a type of kinase inhibitor. It is the third FDA-approved "tissue agnostic"-a type of drug designed to target a common biomarker for cancer across different types of tumors rather than the original location of the tumor itself.

 

Tyrosine receptor kinase (TRK) is a protein that activates signaling pathways in the body, the end result of which is neuronal cell survival, angiogenesis, proliferation, and invasion. These functions are normally kept in check by growth factors. When NTRK genes fuse with unrelated genes, there is an overexpression of the TRK fusion protein. More than two dozen types of cancers with NTRK gene fusions have been identified.

 

Entrectinib has received the FDA's accelerated approval designation and priority review status. The drug was evaluated in four clinical trials of 54 adults with NTRK fusion-positive tumors, including those in the lung, salivary gland, breast, thyroid, and colon/rectum. Fifty-seven percent of patients experienced substantial tumor shrinkage from entrectinib use and 7.4% saw their tumors disappear. Drug safety data were derived from the use of entrectinib in 30 pediatric patients. (Approval for patients 12 years and older is based on efficacy data from adult trials. This is because adolescents are not normally included in traditional drug development until it is well underway or approval for adult use of the drug has been achieved. Accelerated approval allows the use of adult data to determine adolescent efficacy.)

 

Entrectinib was also approved for use in adults with non-small cell lung cancer whose tumors are ROS1 positive (meaning there is a mutation of the ROS1 gene) and the cancer has metastasized. In clinical trials of 51 adults with ROS1-positive lung cancer, 78% saw tumor shrinkage and 5.9% had the cancer disappear.

 

There are several warnings and precautions listed in entrectinib's labeling. These include congestive heart failure, central nervous system effects (cognitive impairment, mood disorders, dizziness, sleep disturbances), skeletal fractures, hepatotoxicity, hyperuricemia, QT interval prolongation, vision disorders, and embryo-fetal toxicity. The most common adverse reactions were fatigue, constipation, distorted taste, edema, dizziness, diarrhea, nausea, distorted sense of touch, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, pyrexia, arthralgia, and vision disorders.

 

Nurses who administer entrectinib should use a drug database to assess for potential drug interactions via the cytochrome P-450 (CYP) pathway. Moderate to strong CYP3A inhibitors and inducers should be avoided because they can alter circulating drug levels. Adolescent doses are based on body surface area, so nurses should carefully assess a patient's current size and weight. Patients should be told to swallow the capsules whole. Patients receiving entrectinib should be assessed for adverse effects; if any occur, the health care team should be consulted, as a dose reduction may be needed. Recommended dose modifications are described in the drug's labeling.

 

For complete prescribing information for entrectinib, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212725s000lbl.pdf.