Rozlytrek（entrectinib）

[indications]
The Food and Drug Administration (FDA) of the United States has accelerated the approval of the targeted anticancer drug Rozlytrek(entrectinib) for pediatric and adult patients with advanced solid tumor with neurotrophic tyrosine receptor kinase (NTRK) gene fusion positive at present.

The medicine can be used for adult patients with ROS1-1 positive metastatic non-small cell lung cancer (NSCLC), whose tumors are adult and child patients with solid tumors aged 12 years and above, who have the gene fusion of neurotrophic tyrosine receptor kinase (NTRK), have no known acquired resistance mutation, metastasis or surgical resection may lead to serious morbidity, and progress or no satisfactory alternative therapy after treatment.

Rozlytrek is a new “broad-spectrum” anticancer drug, which was first approved in Japan in June this year, becoming the first “tumor agnosticism” drug targeted at NTRK gene fusion in this market. NTRK gene fusion has been identified in a series of refractory solid tumor types, including pancreatic cancer, thyroid cancer, salivary adenocarcinoma, breast cancer, colorectal cancer and lung cancer.

“How to use”
Capsule, for oral use.
Recommended dosage of ROS1- positive non-small cell lung cancer: 600 mg per day.
Recommended dosage for NTRK gene fusion positive solid tumor: Adult: 600 mg orally daily.
Pediatrics aged 12 and over: The recommended dosage is based on body surface area (BSA), as follows:
BSA greater than 1.50 m 2：600 mg once a day.
BSA 1.11 to 1.50 m 2: 500mg once a day.
BSA 0.91 to 1.10 m 2: 400 mg once a day.

【 Warning and Precautions 】
1. Congestive heart failure: In patients with CHF or known risk factors, the left ventricular ejection fraction was evaluated before the start of ROZLYTREK. To monitor the symptoms and signs of patients with congestive heart failure (CHF). For patients with myocarditis, MRI or cardiac biopsy may be needed for diagnosis, regardless of whether there is a decrease in ejection fraction. For new or worsening CHF, detain ROZLYTREK, reevaluate LVEF and conduct appropriate medical management. According to the severity of CHF or LVEF deterioration, reduce or stop ROZLYTREK.
2. Systemic (CNS) effect: ROZLYTREK can have adverse reactions of the central nervous system, including cognitive impairment, emotional disorder, dizziness and sleep disorder. Detain and then resume with the same or reduced dosage when improving, or stop ROZLYTREK permanently according to the severity.
3. Fracture: ROZLYTREK increases the risk of fracture. Timely assessment of signs of fracture or.
4. Liver: In the first month, monitor liver examination every 2 weeks, including ALT and AST, and then once a month, and follow the instructions. According to the severity, detain or stop ROZLYTREK forever. If detained, ROZLYTREK will be restored with the same or reduced dosage according to the severity.
5. Hyperuricemia: The serum uric acid level was evaluated before the start, and it was evaluated regularly during the use of ROZLYTREK. Monitor the symptoms and signs of hyperuricemia in patients. If instructed to start with drugs that reduce urate, and keep the signs and symptoms of ROZLYTREK for hyperuricemia. Based on the severity, it will be recovered with the same or reduced dosage when it is improved.
6.QT interval prolongation: monitoring patients at risk of QTc interval prolongation or at risk of QTc interval prolongation. QT interval and electrolyte were evaluated at baseline and regularly during treatment. Detain and then resume with the same or reduced dosage, or stop ROZLYTREK permanently according to the severity.
7. Visual impairment: keep new visual changes or changes, and interfere with daily life activities until they are improved or stabilized. Ophthalmic evaluation as appropriate. Recover with the same or reduced dosage after improvement or stabilization.
8. Embryo-fetus: It may cause fetal injury. Inform women of the potential risks to the fetus and use effective contraceptive measures.

[Adverse reaction]
The most common adverse reactions (≥ 20%) are fatigue, taste disorder, edema, dizziness, diarrhea, nausea, insensitivity, dyspnea, cognitive impairment, weight gain, cough, vomiting, fever, joint pain and visual impairment.