90 Capsules Entrectinib Rozlytrek 200mg Drugs To Treat Lung Cancer

【Drug Name】

Generic name: entrectinib capsules

 

Product name: Rozlytrek®, English product name Rozlytrek®

 

English name: Entrectinib Capsules

 

Chinese Pinyin: Enqutini Jiaonan

 

【Indications】

solid tumors

 

This product is suitable for adults and children aged 12 and above with solid tumors who meet the following conditions:

 

Diagnosis of neurotrophic tyrosine receptor kinase (NTRK) fusion gene by a well-validated test that does not include known acquired resistance mutations,

 

Patients with locally advanced, metastatic disease or in whom surgical resection may result in serious complications, and patients with no satisfactory alternative treatments or in whom previous treatments have failed.

 

This indication has been conditionally approved for marketing based on surrogate endpoints. No clinical endpoint data have been obtained yet, and the effectiveness and safety need to be further confirmed after marketing.

 

Non-small cell lung cancer (NSCLC)

 

This product is suitable for adult patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).

 

【Dosage】

patient choice

 

solid tumors

 

Treatment with this product should be initiated by a physician experienced in anti-cancer treatment.

 

Before treatment with this product, it must be confirmed that the patient's tumor sample carries the NTRK fusion gene. A validated assay should be used to determine a patient's NTRK fusion gene status. Patients who are judged to carry the NTRK fusion gene according to the test results of the hospital or laboratory can receive treatment with this product, and an independent third party designated by Roche must conduct an audit to confirm that the patient indeed has the NTRK fusion gene and can continue to take the drug.

 

Non-small cell lung cancer (NSCLC)

 

Validated assays are needed to select patients with ROS1-positive locally advanced or metastatic NSCLC. ROS1-positive status should be determined before initiating entrectinib treatment.

 

Recommended dosage

 

This product is suitable for oral administration. Hard capsules should be swallowed whole. Because the contents are bitter, they should not be opened or dissolved before taking the medicine. This product may be taken with or without food, but should not be taken with grapefruit or grapefruit juice.

 

Adults: The recommended dose for adults is 600 mg PO once daily.

 

Pediatric Patients: The recommended dose for pediatric patients 12 years of age and older is 300 mg/m2 PO once daily (see Table 1).

 

▼ Table 1: Recommended Dosing Regimen for Pediatric Patients

 

Body Surface Area (BSA) Dosed once daily

1.11-1.50 m2 400 mg

≥ 1.51m2 600 mg

treatment duration

 

It is recommended that patients receive treatment with this product until disease progression or intolerable toxicity occurs.

 

Delayed or missed dose

 

If the patient misses a dose, he or she may take a missed dose unless it is less than 12 hours before the next dose.

 

If the patient vomits immediately after taking entrectinib, the patient can take the drug again.

 

Dosage Adjustment for Adult Patients

 

The entrectinib dose in adults may be reduced up to two times based on tolerability. Table 2 provides general dose adjustment recommendations for adult patients. If a patient cannot tolerate the 200 mg once daily dose, entrectinib therapy should be permanently discontinued.

 

▼ Table 2 Dose reduction plan for adult patients

 

Tapering Plan Dose Level

Starting dose 600 mg once daily

Initial dose reduction 400 mg once daily

Second dose reduction 200 mg once daily

Dosage Adjustment in Pediatric Patients

 

 

Table 3 provides specific dose reduction recommendations for pediatric patients. Pediatric patients 12 years of age and older may undergo dose reductions up to two times based on tolerability.

 

Some pediatric patients require an intermittent dosing regimen to achieve the recommended total dose reduction for one week. Entrectinib therapy should be permanently discontinued if the patient is unable to tolerate the lowest recommended dose after reduction.

 

▼ Table 3 Dose Reduction Scheme for Pediatric Patients

 

measure

BSA 1.11-1.50 m2

 

(once a day)

 

BSA ≥ 1.51 m2

 

(once a day)

 

Recommended dosage

600 mg

First dose reduction 300 mg 400 mg

Second Taper 200 mg 5 days per week* 200 mg

*5 days a week: Monday, Wednesday, Friday, Saturday and Sunday

Dose adjustment after occurrence of specific adverse reactions

 

 

Recommendations for dose adjustments of entrectinib following the occurrence of specific adverse drug reactions in adult and pediatric patients are shown in Table 4.

 

▼ Table 3 Recommended dosage adjustments after specific adverse drug reactions in adult and pediatric patients

 

Adverse drug reaction Severity* Dose adjustment

Anemia or Neutropenia Grade 3 or 4 Withhold entrectinib treatment until recovery to ≤ Grade 2 or baseline, then restart treatment at the original dose or at a reduced dose, as clinically warranted.

Cognitive impairment ≥ grade 2

Withhold entrectinib treatment until recovery to ≤ grade 1 or baseline, then restart treatment with dose reduction.

 

If adverse events recur, reduce the dose again.

 

For prolonged, severe, or intolerable events, consider discontinuing treatment based on clinical status.

 

Transaminase elevation grade 3

Withhold entrectinib therapy until recovery to ≤ Grade 1 or baseline.

 

If recovery occurs within 4 weeks, restart treatment at the original dose.

 

If adverse effects do not resolve within 4 weeks, permanently discontinue treatment.

 

If recurrent grade 3 events resolve within 4 weeks, restart treatment with dose reduction.

 

level 4

Withhold entrectinib therapy until recovery to ≤ Grade 1 or baseline.

 

If recovery occurs within 4 weeks, reduce dose and restart treatment.

 

If adverse effects do not resolve within 4 weeks, permanently discontinue treatment.

 

If grade 4 adverse events recur, treatment is permanently discontinued.

 

ALT or AST elevation >3 × ULN; and total bilirubin elevation >2 × ULN (without cholestasis or hemolysis) Permanently discontinue entrectinib therapy.

Hyperuricemia Symptomatic or Grade 4

Start uric acid-lowering drugs.

 

Withhold entrectinib therapy until signs or symptoms improve.

 

Restart entrectinib treatment at the original dose or at a reduced dose.

 

Congestive heart failure grade 2 or 3

Withhold entrectinib treatment until recovery to ≤ grade 1.

 

Restart treatment after reducing dose.

 

level 4

Withhold entrectinib treatment until recovery to ≤ grade 1.

 

Restart treatment after dose reduction, or discontinue treatment, depending on clinical status.

 

QT interval prolongation QTc 481-500 ms

Withhold entrectinib therapy until recovery to baseline.

 

Restart treatment at original dose.

 

QTc > 500 ms

Withhold entrectinib therapy until the QTc interval returns to baseline.

 

If the cause of QT prolongation is identified and corrected, restart treatment at the original dose.

 

If other unspecified causes of QT prolongation exist, reduce the dose and restart treatment.

 

Torsades de pointes; polymorphic ventricular tachycardia; signs/symptoms of severe arrhythmias. Permanently discontinue entrectinib therapy.

Other clinically significant adverse reactions Grade 3 or 4

Withhold entrectinib treatment until adverse reactions resolve or improve to grade 1 or baseline.

 

If recovery occurs within 4 weeks, restart treatment at the original dose or at a reduced dose.

 

If adverse effects do not resolve within 4 weeks, consider permanently discontinuing treatment.

 

If grade 4 adverse events recur, treatment is permanently discontinued.

 

ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal; QTc = heart rate corrected QT interval

 

*Severity determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

 

Coadministration of strong or moderate CYP3A inhibitors

 

Adults: In adult patients, coadministration with strong or moderate CYP3A inhibitors should be avoided or should be limited to no more than 14 days. If coadministration is unavoidable, the entrectinib dose should be reduced to 100 mg once daily when coadministered with a strong CYP3A inhibitor and to a lower dose when coadministered with a moderate CYP3A inhibitor. to 200 mg once daily. After discontinuation of the coadministered strong or moderate CYP3A inhibitor, entrectinib may be resumed at the preconcomitant dose. CYP3A4 inhibitors with long half-lives may require a washout period.

 

Pediatric Patients: Coadministration of strong or moderate CYP3A inhibitors should be avoided in pediatric patients 12 years of age and older.

 

Concomitant use of CYP3A inducers

 

In adult and pediatric patients, coadministration of CYP3A inducers should be avoided.

 

Dosage Instructions for Special Populations

 

Children: The safety and effectiveness of entrectinib in children younger than 12 years of age have not been established.

 

Geriatric: No entrectinib dose adjustment is required in patients ≥ 65 years of age.

 

Renal Impairment: No dosage adjustment is required in patients with mild or moderate renal impairment. The safety and efficacy of entrectinib have not been studied in patients with severe renal impairment. However, because the renal elimination of entrectinib is negligible, no dose adjustment is required in patients with severe renal impairment.

 

Hepatic Impairment: No dosage adjustments are recommended in patients with mild hepatic impairment. The safety and efficacy of entrectinib have not been studied in patients with moderate to severe hepatic impairment.

 

【Adverse reactions】

 

The most common adverse reactions (≥20%) are fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, hypoesthesia, dyspnea, anemia, weight gain, increased serum creatinine, pain, cognitive impairment, vomiting, Cough and fever.

 

The most common serious adverse reactions (≥2%) were pulmonary infection (5.2%), dyspnea (4.6%), cognitive impairment (3.8%), pleural effusion (3.0%), and fracture (2.4%). 4.6% of patients permanently discontinued treatment due to adverse reactions.

 

【Storage】

Sealed and stored no more than 30℃.