Entrectinib (Rozlytrek) is a targeted anticancer agent indicated for patients with tumors harboring specific gene mutations.

 Indications

Entrectinib is primarily indicated for the treatment of the following two groups of patients:

Adult patients with ROS1-positive non-small cell lung cancer (NSCLC).

(1) Indicated for adult patients with metastatic ROS1-positive NSCLC confirmed by an FDA-approved test.

(2) This agent potently inhibits the kinase activity of ROS1 and blocks tumor growth signaling pathways.

Patients with NTRK gene fusion-positive solid tumors

(1) Indicated for adult and pediatric patients aged 1 month and older with NTRK gene fusion-positive tumors and no known acquired resistance mutations.

(2) Applicable to patients with metastatic tumors or tumors for which surgical resection may result in severe complications, and who have failed prior therapy or lack satisfactory alternative treatment options.

(3) This indication was granted accelerated approval based on tumor response rate and duration of response.

Contraindications and Contraindicated Foods

Contraindications

A comprehensive assessment of the patient's condition is required prior to administration, especially for patients with underlying diseases of the heart, liver, nervous system and other organs.

Contraindicated Foods and Drug Interactions

Grapefruit and its products: Grapefruit inhibits CYP3A enzymes, which can significantly increase the plasma concentration of entrectinib and raise the risk of adverse reactions. Consumption should be avoided during treatment.

Other Contraindicated Drugs

(1) Strong or moderate CYP3A inhibitors (e.g., itraconazole, clarithromycin): Concomitant use should be avoided; if unavoidable, the dosage of entrectinib must be adjusted.

(2) CYP3A inducers (e.g., rifampicin, carbamazepine): May reduce the therapeutic efficacy of entrectinib, and concomitant use should be avoided.

(3) Drugs that prolong the QT interval: Concomitant use may increase the risk of arrhythmias, and a cautious assessment is required.

Administration in Special Populations

Pregnant and lactating women

(1) Entrectinib may cause fetal harm and is contraindicated in pregnant women.

(2) Reproductive-aged females should use effective contraceptive measures during treatment and for at least 5 weeks after the last dose.

(3) Female partners of fertile male patients should also use contraception during the patient's treatment and for 3 months after the last dose.

(4) Lactating women should discontinue breastfeeding until 7 days after the last dose.

Pediatric patients

(1) Entrectinib has been approved for pediatric patients aged 1 month and older with NTRK gene fusion-positive solid tumors; the dosage must be accurately calculated based on body surface area.

(2) Pediatric patients have a higher risk of fractures, and close monitoring for skeletal symptoms is required.

(3) The safety and efficacy of entrectinib in pediatric patients with ROS1-positive NSCLC have not been established.

Geriatric patients

(1) Approximately 25% of patients in clinical studies were aged 65 years and older; however, the available data are limited, and no significant differences in response were observed between geriatric and younger patients.

(2) Administration should be cautiously assessed in combination with the patient's overall health status.

Patients with hepatic or renal impairment

(1) Hepatic impairment: Dosage adjustment is generally not required for patients with mild to moderate hepatic impairment; however, data on administration in patients with moderate to severe hepatic impairment are insufficient, and close monitoring for adverse reactions is necessary.

(2) Renal impairment: Dosage adjustment is not required for patients with mild to moderate renal impairment; no studies have been conducted in patients with severe renal impairment, and cautious use is advised.

Patients with cardiac or neurological diseases

Patients with a history of heart failure, QT interval prolongation, epilepsy, psychiatric disorders and other such conditions should receive entrectinib under close monitoring; dosage adjustment or temporary treatment interruption should be implemented if necessary.