Appeal type: Experimental/Investigational
Decision: Upheld Decision of Health Plan

Physician 1: The patient is a 49-year-old woman who received Taxane-based neoadjuvant therapy prior to mastectomy (pathologic and clinical response not provided) in 2003 and relapsed with lung metastasis six months later.  Her lung was resected and she then received adjuvant chemotherapy with another taxane-based three-drug combination regimen.  The patient had a second lung recurrence two months after her last dose of chemotherapy.  She has now been started on a four-drug combination regimen that includes Avastin, Xeloda, Abraxane and Tarceva. The Health Plan authorized chemotherapy with Abraxane and Zometa, but has denied authorization for Avastin based upon their determination that the four-drug combination of Avastin, Xeloda, Abraxane and Tarceva is experimental/investigational in this clinical context.The use of a four-drug chemotherapy regimen in the treatment of metastatic breast cancer is not the current standard of care.  In general, we are just beginning to see a few Phase III trials that support selected two-drug regimens over single sequential drugs.  There is one published Phase III study presented at the 2005 ASCO conference that showed a benefit when bevacizumab was combined with a taxane, but this was as a first-line therapy for patients who had not been previously treated for metastatic cancer with a taxane.  This is clearly distinguished from third-line therapy with a third taxane as is the case with this patient.  Additionally, the increased risk of thromboembolic disease and added toxicity argue against the proposed four-drug combination.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 49-year-old woman with metastatic breast cancer.  She received neoadjuvant chemotherapy consisting of Cytoxan, Adriamycin, and Taxotere and had a six-month disease free interval ending with a recurrence in her right lung.  Following a resection of the lesion she was treated with carboplatin, Navelbine and Taxol.  There was a second recurrence within two months of that therapy and her disease has progressed. The patient began treatment with a four-drug combination regimen of Avastin, Xeloda, Abraxane and Tarceva. The Health Plan considers the four-drug regimen investigational and has denied authorization and coverage for the therapy.  They have instead authorized treatment with Abraxane and Zometa.A search of the medical literature revealed no peer-reviewed data supporting this four-drug combination regimen and confirms the investigational nature of this treatment approach. The Miller study is not directly on point as the participants of that study were disease free for a 12-month interval and realized a benefit from Avastin as a first line treatment for metastatic disease.  Additionally, there is no data on the efficacy of Xeloda and Avastin in heavily treated patients and there is no safety data on this specific four-drug combination. 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 49-year-old woman with Stage IV breast cancer with lung metastasis recurrent after first and second-line chemotherapy. She is appealing the denial of Avastin as part of a multi-agent regimen that includes Abraxane, a modified taxane. The Health Plan has denied coverage due to the lack of data that this Avastin-associated therapy has any proven benefit.Determining the efficacy and timing of immunochemotherapy is a rapidly evolving and often controversial field.  However, in toto, there is growing evidence that anti-angiogenesis therapy, and specifically Avastin, when combined with taxane chemotherapy impacts the clinical progression of disease in poor-prognosis/heavily pre-treated breast cancer patients. This theme continued to be evident at the recently concluded San Antonio Breast Cancer Conference (December 2005).  The peer-reviewed literature is not particularly illuminating at present. There are two published contradictory studies regarding survival benefit. Given the length of time that large clinical trials in a generally responsive breast cancer population take to complete, this is not unusual.  Several interim analyses of large, on-going trials and completed smaller studies do support a role for Avastin in this clinical setting. Under these circumstances, in a young patient with adequate performance status, and metastatic hormone-refractory breast cancer, who is tolerating the regimen and appears to be benefiting from this therapy, a trial of a taxane and Avastin would be considered a reasonable intervention.Based upon the information set forth above, I have determined that the requested therapy is likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be overturned.