Appeal type: Experimental/Investigational
Decision: Upheld

Physician 1:  This patient is a 62-year-old male diagnosed with hepatocellular carcinoma in July 2004. The tumor was resected and no further treatment was provided at that time. The patient did well until November 2005 when he was found to have an abdominal nodule positive for recurrence.  CT and PET scans revealed multiple lung metastases. He was treated with an investigational agent, which did not halt the progression of his disease.  In April 2006 the patient began chemotherapy with cisplatin, 5-FU, interferon and Avastin. The patients request for reimbursement and prospective authorization for Avastin and interferon was denied by the Health Plan citing the experimental/investigational nature of the therapy.Overall chemotherapy has been of little benefit in metastatic hepatocellular carcinoma. Although interferon has been used in the presence of hepatitis C in an effort to prevent hepatocellular carcinoma, it is not known to be effective in the actual treatment of metastatic hepatocellular carcinoma. Similarly, there is no clinical data on the efficacy of Avastin in the treatment of hepatocellular carcinoma.  A number of articles were submitted on behalf of the patient. The majority have no relevance to the proposed treatment and others are theoretically relevant, but without clinical data to support the use of interferon and/or Avastin for treatment of the patients disease. Therefore, I have determined that the therapy at issue is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be upheld.Physician 2:  The patient is a 62-year-old male with hepatocellular carcinoma diagnosed in July 2004 and initially treated with resection of the right lobe of the liver.  Recent metastatic disease was recognized by chest CT as extensive bilateral pulmonary lesions, peritracheal adenopathy and bilateral hilar masses.  The tumor has progressed despite experimental treatment with compound GW 572016.  The patients current chemotherapy regimen includes cisplatin, 5-flourouracil, alpha interferon and Avastin.  He has requested reimbursement for past treatment and future authorization and coverage of the Avastin and interferon. The Health Plan has determined that the use of these agents for the treatment of metastatic hepatocellular carcinoma remains unproven and therefore the patients request was denied.No clinical trial has been published evaluating the use of this regimen as treatment for metastatic hepatocellular carcinoma; therefore efficacy has not been established.  The patients current chemotherapy regimen includes drugs with significant side effects, and in combination, these side effects may be compounded.  The patient was extremely ill during the first cycle of chemotherapy.  As the effectiveness of this therapy has not been clinically established and there is reasonable evidence of the untoward effects, I have determined that the therapy at issue is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be upheld.Physician 3:  The patient is a 62-year-old male with Stage IV hepatocellular carcinoma (HCC).  He recently completed one cycle of chemo-immunotherapy, which included the requested agents, interferon and Avastin.  The patient was hospitalized with intractable nausea, requiring hyperalimentation support due to cachexia. The patient has requested reimbursement and continued authorization and coverage for the immunotherapy (interferon and Avastin). The Health Plan has denied the request based upon a determination that the therapy is experimental/investigational in this clinical setting.Metastatic HCC is invariably associated with poor outcomes.  In advanced disease, meaningful therapy is impeded by poor performance status, and is often governed by the degree of hepatic dysfunction. The patients hospitalization after one cycle of combination chemo-immunotherapy is informative as to his poor performance status, but the record did not include data related to hepatic function.   Although anti-angiogenic therapy (Avastin) and immunomodulation (interferon) have been used in several solid tumor histologies, the safety and efficacy in metastatic HCC has not been convincingly demonstrated in the peer-reviewed literature.  This therapeutic regimen is not included in treatment guidelines/reviews such as NCCN or UpToDate expert reviews which are widely accepted in the oncology community. Although there is no established standard of care for advanced HCC, a consistent theme in the literature and in clinical experience is the need to carefully weigh the status of the patient, the tolerability and the life expectancy benefit of the potential regimen against the need to undertake new combinations/modalities in the context of a clinical scenario with a poor prognosis.  The extrapolation of the results of immunomodulatory and/or anti-angiogenic agents reported in peer-reviewed literature is not informative in a patient with poor performance status and widespread disease.  Based on the clinical factors involved, I have concluded that the therapy at issue is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be upheld.