REPOTRECTINIB CAP,ORAL
Clinical Criteria Summary
Indications & Patient Population
- Locally advanced or metastatic ROS-1 fusion positive non-small cell lung cancer (NSCLC)
- Solid tumors with a neurotrophic tyrosine receptor kinase (NTRK) gene fusion with locally advanced or metastatic disease where surgery would cause morbidity, progressed following treatment, or have no satisfactory alternative therapy
- Adult and pediatric patients (≥12 years) with an ECOG performance status ≤1
Dosing & Administration
- 160 mg capsules taken orally once daily for 14 days, then increased to twice daily
- Available in 40 mg and 160 mg capsule strengths
Pretreatment & Monitoring Requirements
- Pretreatment serum uric acid assessment indicated
Safety Considerations Impacting Use
- CNS adverse reactions (dizziness, ataxia, cognitive impairment) occurred in 77% of patients
- Interstitial lung disease/pneumonitis reported in 3.1%
- Hepatotoxicity observed with increased ALT (38%) and AST (41%)
- Myalgia occurring in 13%, sometimes with CPK elevation
- Hyperuricemia reported in 5%
- Skeletal fractures occurred in 2.3% of adult patients
- Grade 3 or 4 adverse reactions occurred in 45%; serious adverse reactions in 35% (most common: pneumonia, dyspnea, pleural effusion)
- Permanent discontinuation due to adverse reactions occurred in 7%
Drug Interactions
- Avoid concomitant use with strong or moderate CYP3A inhibitors, P-gp inhibitors, and strong or moderate CYP3A inducers
- Repotrectinib acts as a CYP3A4 inducer and may reduce efficacy of CYP3A4 substrates
- Avoid concomitant use with hormonal contraceptives
Pregnancy & Lactation
- Can cause fetal harm
- Advise lactating women to discontinue breastfeeding during treatment and for 10 days after the last dose
Place in Therapy & Clinical Guidelines
- NCCN guidelines list as preferred first-line option for ROS1 gene fusion in NSCLC alongside crizotinib, entrectinib, or taletrectinib
- NCCN guidelines list as preferred first-line option for NTRK gene fusion in solid tumors alongside entrectinib or larotrectinib
- Next-generation TKIs (including repotrectinib) offer improved progression-free survival, better CNS penetration, and activity against resistance mutations compared to first-generation TKIs
- VA Clinical Pathway currently lists entrectinib for ROS1 fusion positive NSCLC and NTRK fusion positive NSCLC
- Consider taletrectinib for advanced ROS1 fusion positive NSCLC and larotrectinib for NTRK fusion positive solid tumors (NSCLC)