Stivarga

Metastatic colorectal cancer (CRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and anti-EGFR therapy (if KRAS wild-type); Locally advanced, unresectable, or metastatic gastrointestinal stromal tumors (GIST) previously treated with imatinib and sunitinib; Hepatocellular carcinoma (HCC) previously treated with sorafenib

160 mg orally once daily (four 40 mg tablets) for the first 21 days of each 28-day cycle
Take with food (low-fat breakfast containing less than 30% fat)
Dose reductions: 120 mg, then 80 mg

Tablets: 40 mg

None listed.

• Hepatotoxicity: Fatal hepatic failure reported. Monitor LFTs at baseline, at least every 2 weeks during first 2 months, then monthly. Interrupt for AST/ALT >5× ULN or >3× ULN with concurrent bilirubin >2× ULN.
• Infections: Fatal infections reported. Withhold for Grade 3-4 infections.
• Hemorrhage: Fatal hemorrhage reported. Permanently discontinue for severe/life-threatening hemorrhage.
• GI Perforation/Fistula: Discontinue permanently.
• Dermatologic Toxicity: Hand-foot skin reaction (HFSR) in up to 53% (CRC). Dose modify for Grade 2+ HFSR.
• Hypertension: Monitor BP weekly for first 6 weeks.
• Cardiac Ischemia/Infarction: Withhold for new/acute cardiac events.
• Posterior Reversible Encephalopathy Syndrome (PRES)
• Wound Healing: Stop at least 2 weeks before surgery.

Hand-foot skin reaction (53%), fatigue (47%), diarrhea (43%), hypertension (30%), decreased appetite (30%), oral mucositis (29%), dysphonia (29%), infection (21%), weight loss (14%), rash (18%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Regorafenib is a small-molecule inhibitor of multiple membrane-bound and intracellular kinases including those involved in tumor angiogenesis (VEGFR1-3, TIE2), oncogenesis (KIT, RET, RAF1, BRAF, BRAFV600E), metastasis (VEGFR3, PDGFR, FGFR), tumor immunity (CSF1R), and the tumor microenvironment (PDGFR, FGFR).

Tmax: approximately 4 hours. Half-life: 28 hours (parent), 51 hours (M-2 metabolite), 59 hours (M-5 metabolite). Both metabolites pharmacologically active. Protein binding: 99.5%. Metabolized by CYP3A4 and UGT1A9. Excreted in feces (71%) and urine (19%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• CORRECT — Regorafenib vs. placebo in metastatic CRC after standard therapies. Phase III, n=760.
  🔬 NCT01103323 ↗ 📄 Primary Publication ↗
• RESORCE — Regorafenib vs. placebo in HCC after sorafenib. Phase III, n=573.
  🔬 NCT01774344 ↗ 📄 Primary Publication ↗

Stivarga has FDA-approved indications across the following cancer types covered on PipelineEvidence: