Repotrectinib (Augtyro) is a novel kinase inhibitor that received its first approval in the United States in 2023. This medication is primarily indicated for the treatment of ROS1-positive non-small cell lung cancer (NSCLC) and NTRK gene fusion-positive solid tumors.

How to Use Repotrectinib (Augtyro)

Patient Selection Criteria

For locally advanced or metastatic ROS1-positive NSCLC: Patients are selected based on the presence of ROS1 rearrangement in tumor specimens.

For locally advanced or metastatic solid tumors: Patients are selected based on the presence of NTRK1/2/3 rearrangement in tumor specimens.

For secretory breast carcinoma or breast carcinoma with secretory features, treatment may be considered without confirming NTRK rearrangement in tumor specimens.

Recommended Dosage Regimen

Initiation phase: 160 mg orally once daily for 14 consecutive days.

Maintenance phase: Increase to 160 mg orally twice daily.

Administration method: May be taken with or without food.

Duration of Treatment

Continue treatment until disease progression or the occurrence of unacceptable toxicities.

Dosage Adjustment of Repotrectinib (Augtyro)

Dosage Adjustment for Adverse Reactions

First dose reduction: Adjust from 160 mg twice daily to 120 mg twice daily.

Adjust from 160 mg once daily to 120 mg once daily.

Second dose reduction: Adjust from 120 mg twice daily to 80 mg twice daily.

Adjust from 120 mg once daily to 80 mg once daily.

Central Nervous System (CNS) Reactions

Intolerable Grade 2: Temporarily discontinue medication until improvement to ≤ Grade 1 or baseline, then resume at the same dose or a reduced dose.

Grade 3: Temporarily discontinue medication until improvement to ≤ Grade 1 or baseline, then resume at a reduced dose.

Grade 4: Permanently discontinue medication.

Hepatotoxicity Reactions

Grade 3: Temporarily discontinue medication until improvement to ≤ Grade 1 or baseline.

If resolved within 4 weeks, resume at the same dose.

If a recurrent Grade 3 event resolves within 4 weeks, resume at a reduced dose.

Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 3 times the upper limit of normal (ULN) with total bilirubin > 1.5 times ULN: Permanently discontinue medication.

Use of Repotrectinib (Augtyro) in Special Populations

Patients with Hepatic Impairment

Mild hepatic impairment: No dosage adjustment is required.

Moderate or severe hepatic impairment: A recommended dosage has not been established.

Patients with Renal Impairment

Mild or moderate renal impairment: No dosage adjustment is required.

Severe renal impairment or renal failure: A recommended dosage has not been established.

Pregnancy

Repotrectinib may cause fetal harm.

Females of reproductive potential are advised to use effective non-hormonal contraceptive methods.