FRUQUINTINIB CAP,ORAL

Clinical Criteria Summary

Metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, and anti-VEGF therapy/RAS wild-type anti-EGFR therapy if medically appropriate.
Patients who have exhausted all standard treatment options including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, an anti-EGFR therapy (if RAS wild-type), and progressive disease or intolerance to trifluridine-tipiracil (with or without bevacizumab).
Heavily pretreated patients who have exhausted all other viable lines of therapy including fluoropyrimidine, oxaliplatin, irinotecan, anti-EGFR inhibitor, anti-VEGF, trifluridine/tipiracil or regorafenib-based therapy.

5mg PO daily for days 1-21 of a 28-day cycle until progression of disease or intolerable toxicity.
Available as oral capsules: 5mg & 1mg.

Age 18-75 years
Histologically and/or cytologically confirmed metastatic colorectal cancer
Progression on/intolerant of at least two prior lines of standard therapy (including fluoropyrimidine, oxaliplatin, irinotecan, anti-EGFR, anti-VEGF therapies) or progressive disease or intolerance to trifluridine/tipiracil and/or regorafenib therapy
Body weight ≥ 40kg
ECOG Performance status ≤ 1
Life expectancy > 12-weeks

Prior use of VEGF inhibitor (excluding bevacizumab)
Baseline cytopenias, liver dysfunction, renal dysfunction, proteinuria, uncontrolled hypertension, uncontrolled infection, or significant electrolyte abnormality
CNS metastases
Persistent grade >1 toxicity from prior treatment (excluding neuropathy grade ≤2)
History severe bleed or thromboembolic events within 6-months

Hypertension: Adjust anti-hypertensive therapy as appropriate; hold/discontinue if control cannot be achieved.
Hemorrhagic Events: Permanently discontinue if serious hemorrhage occurs.
Infections: Hold for grade 3-4 infections and resume after resolution.
Gastrointestinal Perforations: Permanently discontinue if occurs.
Hepatotoxicity: Hold and adjust depending on severity and persistence.
Proteinuria: Hold and adjust depending on severity and persistence.
Palmar-Plantar Erythrodysesthesia (PPE): Hold and adjust depending on severity and persistence.
Posterior Reversible Encephalopathy Syndrome (PRES): Permanently discontinue if develops.
Impaired Wound Healing: Do not give within 2 weeks of a major surgery.
Arterial Thromboembolic Events: Exercise caution in patients with recent thromboembolic events.
Allergic Reactions to FD&C Yellow No. 5 & No. 6: Note sensitivity more frequently seen in those with aspirin allergy (dyes only present in 1mg capsule).
Embryo-Fetal Toxicity: Avoid during pregnancy and take precautions to avoid conception while on treatment.
Drug Interactions: Avoid concomitant use with strong or moderate CYP3A inducers as they may decrease efficacy.

Designated as a 3rd line therapy for advanced/metastatic colorectal cancer for patients who would not qualify for anti-EGFR therapy.
Replaced regorafenib in the VHA pathway; follows trifluridine-tipiracil.
NCCN Guidelines Category 2A recommendation for advanced/metastatic colorectal cancer that has progressed through fluoropyrimidine, oxaliplatin, irinotecan, EGFR targeting (if appropriate), and other biomarker directed therapy.
Considered a more tolerable 3rd line agent for mCRC due to toxicity profile limitations of regorafenib.

Unmanageable drug-drug interaction
Severe renal impairment (creatinine clearance < 30 mL/min)
Baseline proteinuria (Protein of ≥2g on urinalysis/24 hours or 24-hour urine protein of ≥ 1.0g)
Moderate or severe hepatic impairment (total bilirubin > 1.5 times the Upper Limit of Normal, unless with Gilbert syndrome)
Uncontrolled hypertension
Major surgery within 2 weeks or until adequate wound healing has been achieved
Pregnancy
Lactating

Care is provided by a VA/VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Goals of care and role of Palliative Care consult have been discussed and documented

Diagnosis of metastatic colorectal cancer
Received prior treatment with or is not a candidate to receive a fluoropyrimidine-based regimen
Received prior treatment with or is not a candidate to receive an oxaliplatin-based regimen
Received prior treatment with or is not a candidate to receive an irinotecan-based regimen
If KRAS wild type, received an anti-EGFR agent (i.e. cetuximab or panitumumab)
Received prior treatment with or is not a candidate to receive trifluridine-tipiracil with or without bevacizumab

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 2 weeks after the last dose