Regorafenib (Stivarga®) in the Treatment of Hepatocellular Carcinoma

Written by: Jody Agena, PharmD, Virginia Cancer Specialists
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Description: Understand how to identify eligible patients and manage adverse effects of regorafenib treatment in hepatocellular carcinoma.

Background: Regorafenib is a kinase inhibitor indicated for the treatment of patients (Childs Pugh A) with Hepatocellular Carcinoma (HCC) who have been previously treated with sorafenib.  In the phase III – RESORCE Trial, regorafenib was assessed in patients with HCC who have progressed on sorafenib and concluded that there was an improved overall survival compared to placebo (10.6 months vs. 7.8 months). This study also portrayed the difficulties of maintaining therapy, as the discontinuation rate due to adverse events within the treatment arm was observed at 25% and 43% due to progression. The most common grade (all grade) adverse events occurring more frequently in the regorafenib group included:  Hand-foot skin reaction (51%), asthenia/ fatigue (42%), diarrhea (41%), and hypertension (31%). In addition to regorafenib, other 2nd line options include nivolumab.  Patients that are not eligible for nivolumab may include those with comorbidities including but not limited to: pneumonitis, thyroid disorders, renal dysfunction, colitis, previous transplants.

PQI Process: Consider reviewing all current HCC patient in EMR for appropriateness of regorafenib therapy
Upon receipt of a new prescription for Regorafenib:

  • If the typical starting dose of 160 mg by mouth once a day is written, consider initiating dose titration based on the mCRC ReDos trial in metastatic colorectal cancer (mCRC)
    • Initiate patient at 80 mg for the first week of cycle 1
    • If no significant drug-related toxicities, escalate to 120 mg for the second week of cycle 1, otherwise hold therapy at current dose
    • If no significant drug-related toxicities, escalate to 160 mg for the third week of cycle 1, otherwise hold therapy at current dose
    • For following cycles, start therapy at current tolerated dose (no dose escalation)
  • Coordinate and establish a weekly follow up call with the patient or caregiver for the first 8 weeks
  • Monitor baseline LFTs
  • CBC with differential and platelets and serum electrolytes at baseline and monthly
  • Monitor blood pressure weekly for the first 6 weeks of therapy, then every cycle
  • Monitor for hand-foot skin reaction (HFSR) weekly for 2 cycles, then every cycle
  • Monitor for signs/symptoms of cardiac issues, bleeding, GI perforation or fistula, infection, and/or neurological symptoms
  • Monitor for impaired wound healing – Hold medication for 2 weeks prior to surgery to allow proper wound healing
  • Consider providing urea base moisturizer
  • Consider use of anti-diarrheals

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) Sheet
    • Emphasize counseling on side effect table
    • Educate patients on side effects and report adverse effects to prescriber and recommend dose adjustments in 40 mg increments as tolerated
    • Dosing is once daily for 3 weeks on therapy then 1 week off therapy per cycle
    • Medication expires 7 weeks after opening bottle
      • Packaging now available in 21 count bottle
    • Take dosage with low fat meal (< 600 calories)
      • Examples of Low Fat food choices5
        • Dairy and dairy-like products
          • Low-fat (1%) or fat-free (skim) yogurt, cottage cheese, or milk
          • Fat-free American cheese or other types of fat-free cheeses
        • Fish, meat, poultry, and other protein
          • Egg whites or egg substitutes
          • Crab, white fish, shrimp, and light tuna (packed in water)
          • Chicken and turkey breast (without skin), or ground turkey breast
          • Beans, peas, and lentils, cooked (or canned) without added fats
        • Grains, cereals, and pastas
          • Hot (oatmeal or grits) and cold cereals (except granola types)
          • Whole grain brown rice or noodles (watch out for fat in added sauces)
          • Whole grain bagels, pita bread, or English muffins
          • Low-fat crackers and breads
          • Soft tortillas – corn or whole wheat
        • Fruits- including fresh, frozen, or canned (in their own juice)
        • Vegetables- including fresh, frozen, or canned (choose lower-sodium varieties)
        • Other foods
          • Broth type soups with a vegetable base
          • Sauces, pudding, or shakes made with skim milk


  1. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Bruix, Jordi et al. The Lancet, Volume 389 , Issue 10064 , 56 – 66.
  2. Ou FS, Bekaii-Saab T. ReDOS* trial presented at the ASCO GI Cancers Symposium 2018. ReDOS poster from ASCO GI, Jan. 2018.
  3. NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines®) for colon cancer v.2.2018. © Page COL-D 9 of 10. National Comprehensive Cancer Network 2018. All rights reserved.
  4. Bekaii-Saab T, Ou FS, Ciombor KK, et al. Regorafenib dose optimization study (ReDOS): A phase II randomized study of lower starting dose regorafenib compared to standard dose regorafenib in patients with refractory metastatic colorectal cancer (mCRC). Journal of Clinical Oncology 2016 34:15_suppl, TPS3630-TPS3630.
  5. STIVARGA® (Regorafenib) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals.
  6. https://www.cancer.org/healthy/eat-healthy-get-active/take-control-your-w.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.

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