TIVOZANIB CAP,ORAL

Clinical Criteria Summary

Active or untreated central nervous system metastases
Hepatic insufficiency (i.e., total bilirubin > 3 to 10 x ULN with any AST)
Significant cardiovascular disease (i.e., symptomatic left ventricular heart failure, uncontrolled hypertension with systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg, acute coronary syndrome within past 6 months)
Pregnancy (i.e., known pregnancy or positive pregnancy test) or lactating
Concomitant CYP3A4 inducers (strong)

Care provided by a VA/VA Community Care hematology or oncology provider
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

Metastatic renal cell carcinoma with a clear cell component
Previously unsuccessful treatment with 2 or 3 systemic therapy regimens, 1 of which were vascular endothelial growth factor receptor inhibitors other than tivozanib
For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for one month after stopping treatment

Advanced or metastatic renal cell carcinoma (RCC) with clear cell component
Relapsed following two or more prior systemic therapies (specifically after 2 or 3 prior regimens including at least one VEGFR inhibitor other than sorafenib or tivozanib)
ECOG performance status 0-1
Reserved for patients ineligible for or unable to tolerate other preferred systemic therapy options (lenvatinib/everolimus, cabozantinib, nivolumab)
Selection of 3rd or 4th line therapy may be based on patient-specific factors including comorbidities, toxicity profile, dosing frequency (once daily vs twice daily), schedule (daily vs 21 out of 28 days), and drug-drug interaction potential

Hypertension: Monitor; median time to onset is 2 weeks. Not studied in patients with systolic BP >150 mmHg or diastolic BP >100 mmHg.
Cardiac effects: Monitor for cardiac ischemia and failure. Not studied in patients with symptomatic cardiac failure within 6 months prior to therapy.
Hemorrhage: Not studied in patients with significant bleeding within 6 months prior to therapy.
Nephrotoxicity/Proteinuria: Monitor; risk of acute kidney injury noted.
Reversible posterior leukoencephalopathy syndrome (RPLS): Evaluate by MRI if seizures, headaches, visual disturbances, confusion, or altered mental function present.
Thromboembolism: Not studied in patients with arterial thrombotic event, myocardial infarction, or unstable angina within 6 months prior to therapy.
Thyroid disorders: Monitor for hypothyroidism and hyperthyroidism.
Wound healing complications: Monitor due to VEGFR inhibition mechanism.

Geriatric: No overall differences in safety observed compared to patients <65 years.
Renal impairment: No dose modifications recommended for mild to severe impairment (CrCl 15-89 mL/min). Dosage not established for end-stage renal disease (CrCl <15 mL/min).
Hepatic impairment: No dose modification for mild impairment (total bilirubin < ULN with AST >ULN or total bilirubin >1-1.5x ULN with any AST). Reduce dose for moderate impairment (total bilirubin >1.5-3x ULN with any AST). Dosage not established for severe impairment (total bilirubin >3-10x ULN with any AST).
Pregnancy: Verify pregnancy status prior to treatment. Use effective contraception during therapy and for 1 month after the last dose.
Breastfeeding: Not recommended during therapy and for 1 month after the last dose due to potential for serious adverse reactions in the breastfed infant.

Hepatitis B Virus: Consider screening prior to tivozanib due to risk of HBV infection reactivation with anti-cancer agents.
CYP3A4 Inducers: Avoid concomitant use of strong CYP3A4 inducers. Monitor for decreased effect with moderate CYP3A4 inducers.