Appeal type: Experimental/Investigational
Decision: Upheld

Physician #1  :The patient is a 52-year-old female who is requesting authorization and coverage for the use of Avastin as an additional modality to be administered along with carboplatin and gemcitabine to treat stage IV adenocarcinoma of the lung with known brain metastasis (treated with gamma knife radiation). The Health Plan has denied her request on the basis that the use of Avastin in this clinical setting is considered experimental.There is a reported, but not yet published, Phase III trial of Avastin with carboplatin and Taxol as first line therapy that showed modest improvement in survival. This trial excluded subjects with brain metastases because of fear of intracranial bleeding precipitated by Avastin. Indeed, there was a four-fold higher incidence of major bleeding in the trial. In addition, the chemotherapy used in that trial was different from the chemotherapy regimen requested here. For the requested regimen, there is no reported experience at all in lung cancer, possibly due to concerns that the regimen of carboplatin/gemcitabine is associated with increased grade 4 thrombocytopenia, potentially markedly increasing the risks of bleeding either systemically or intracranially. In view of the above stated concerns of increased and serious potential for side effects, and the lack of demonstrated benefit of Avastin used with this chemotherapy regimen, the requested therapy cannot be recommended. Further randomized, prospective, controlled clinical trials are needed before such treatment can be considered within appropriate standard of treatment.Based upon the information set forth above, I have determined that the requested therapy 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 52-year-old female with stage IV adenocarcinoma of the lung. The disease has progressed and brain and bone metastasis has occurred. She is currently receiving carboplatin and Gemzar. Her provider has recommended the addition of Avastin to her regimen. The Health Plan has determined that the use of Avastin remains unproven for the treatment of lung cancer and therefore has denied coverage for the therapy.  Avastin is not being used/has not been shown to overcome intrinsic or acquired resistance to cytotoxic drugs. While it may be safe to use in patients with SRT-treated brain metastasis, it is not appropriate to add the agent to a regimen that has not been effective. The benefits of Avastin were shown in upfront combination with carboplatin and Taxol; Avastin was not shown to be effective in reversing what appears to be acquired resistance.  Standard therapies applicable in this case include radiation therapy to the humerus if the patient is at risk of fracture, and whole brain radiation therapy if additional lesions occur in the brain. In addition, pemetrexed or Taxotere may be appropriate as secondary treatment if the patients brain and bone disease are adequately controlled or asymptomatic. These standard methods are likely to be more efficacious and carry less risk than treatment with Avastin. Therefore, I have determined that the requested therapy 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 52-year-old woman with stage IV non-small cell cancer of the lung (NSCCL) with metastatic disease to the brain and bones. She is appealing denial of coverage for Avastin in combination with chemotherapy. The Health Plan has classified this approach as experimental/investigational.There is evidence for the efficacy of Avastin as a component of first-line chemo-immunotherapy for stage IV lung cancer patients.  However, the exclusion of patients with central nervous system (CNS) disease in the Phase II trials was subsequent to a clinically devastating CNS hemorrhage in a patient with CNS disease in the Phase I trials of Avastin. The efficacy of Avastin has always been balanced with the known tendency for a bleeding dyscrasia associated with use of this drug. The NCCN practitioner guidelines also exclude patients with CNS disease from Avastin therapy.  There is no data to evaluate the potential risk that the patient faces during Avastin therapy; therefore, quantitation of the risk/benefit ratio is not possible. In light of these circumstances, there is no valid evidence that given the widely acknowledged risk of hemorrhage in this setting (a devastating CNS complication), Avastin is likely to be more beneficial to the patient than available standard treatment, which would likely be a trial of a different chemotherapy regimen.  For the reasons set forth above, I have determined that the requested therapy 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.