Using Sorafenib in Advanced HCC


Anthony El-Khoueiry, MD:This patient presents with advanced disease in the sense that she had main portal vein invasion, and, certainly, the presence of main portal invasion with well-preserved liver function is an indication for treatment with sorafenib. This is typical of patients that were included in the SHARP and Asia-Pacific trials. The majority of the patients either had portal vein invasion or extrahepatic metastases, with a small subgroup of patients who had BCLC stage B—meaning disease that’s limited to the liver without portal vein invasion without extrahepatic metastases—but had failed all local-regional modalities. Those would also be appropriate patients for systemic therapy with sorafenib.

This patient, if we go back to the case, had significant adverse events from sorafenib, initially a grade 3 hand-foot-skin reaction and then grade 3 diarrhea. My general dosing strategy is to start with the full dose of sorafenib, 400 mg/twice daily, as long as the patient has Child-Pugh grade A cirrhosis and a well-preserved performance status. However, I do recommend that patients be monitored very closely during the first 4 to 6 weeks and, if they have grade 1 or 2 adverse events that are related to sorafenib, that aggressive supportive care be instituted early on, including loperamide for diarrhea, adjustment of their diet, supportive care measures for anorexia, and topical therapy with urea-based creams for early hand-foot-skin reaction.

However, if—despite all these supportive care modalities—patients have intolerable toxicity or grade 3 events, treatment should be held temporarily until recovery to grade 1 or baseline, and then the therapy with sorafenib should be reinstituted with a dose reduction. The classic dose reduction goes from 400 mg/twice daily to 400 mg/once daily, and then the second dose reduction would be to 400 mg/every other day, as was done in this case.

This patient was continued on sorafenib until she had verifiable radiologic progression with the development of new extrahepatic disease. But, generally, the question is when to discontinue systemic therapy. The indications are when there is verifiable radiologic progression that is not questionable, there is definitive clinical deterioration related to clinical progression of the disease, or there is a clinical decompensation of their liver cirrhosis that would render treatment unsafe or that makes the benefit from the treatment questionable. So, these would be the general indications for treatment discontinuation with systemic therapy.

Transcript edited for clarity.

January 2017

  • A 74-year old female with a history of HCV-infection
  • Prior treatment with interferon, achieving sustained virologic response
  • Had recurrence of HCV
  • CT scan showed a 6.5-cm single liver mass with arterial enhancement, venous phase washout, and main portal vein invasion
  • ECOG=1
  • Child-Pugh A
  • Therapy was initiated with sorafenib at 400 BID
  • Patient experienced grade 3 hand-foot skin reaction; dose reduction to 400 QD
  • Patient experienced grade 3 diarrhea; dose reduction to 400 QOD

April 2017

  • Follow-up scans show radiographic progression with lung metastases
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