RIPRETINIB TAB

Clinical Criteria Summary

CrCl <30 mL/min
Moderate Hepatic Insufficiency defined as total bilirubin > 1.5 × ULN and any AST
Clinically significant cardiovascular disease such as CHF (NYHA Class II to IV), active ischemia and/or angina Pectoris, baseline Left Ventricular Ejection Fraction < 50%
Uncontrolled hypertension, ensure blood pressure control prior to starting therapy
Major surgical procedure within prior 14 days or presence of active wound
Pre-existing bleeding or coagulopathy
Untreated brain metastases
Hypersensitivity to ripretinib
Unmanageable drug interaction with CYP3A inducers and/or inhibitors
Pregnancy (known pregnancy or positive pregnancy test)
Breastfeeding

Care is provided by a VA/VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Goals of care and role of Palliative Care consult have been discussed and documented
Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs. benefits of treatment. Use effective contraception during therapy and for one week after the last dose.

Patients with gastrointestinal stromal tumors who have progressed or have unacceptable toxicity on three prior lines of therapy that includes imatinib, sunitinib, and regorafenib

Adult patients with advanced gastrointestinal stromal tumor (GIST)
Patients who have received prior treatment with 3 or more kinase inhibitors, including imatinib
Patients who have progressed on or are intolerant to three or more tyrosine kinase inhibitors (TKIs), including imatinib

Tablets: 50 mg
Standard dose: 150 mg orally once daily with or without food
Dose escalation: 150 mg twice daily for patients previously treated with 150 mg daily (fifth-line and beyond)

Assess cardiac function prior to initiating therapy
Assess ejection fraction by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) prior to initiation
Monitor blood pressure prior to starting therapy
Ensure hypertension is adequately controlled before starting treatment
Withhold ripretinib at least 1 week prior to elective surgery; do not administer for at least 2 weeks following surgery or until wound is healed
Monitor frequently for adverse reactions when coadministered with strong CYP3A4 inhibitors

Do not initiate in patients with uncontrolled hypertension
Discontinue if Grade 3 or 4 left ventricular systolic dysfunction occurs
Advise women of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose due to embryo-fetal toxicity risk
Advise patients not to breastfeed during treatment and for one week after the final dose
Withhold ripretinib and resume at the same or reduced dose based on severity for palmar-plantar erythrodysesthesia syndrome (PPES)
Advise patients to immediately report any change in or development of new skin lesions due to risk of new primary cutaneous malignancies

NCCN guidelines: Preferred fourth-line therapy (Category 1) for GIST after three prior regimens including imatinib
UpToDate: Recommended for patients with GIST who have progressed on or are intolerant to three or more TKIs, including imatinib
Formulary status: TBD