Nexavar Covered Medication Sorafenib (Nexavar)

What it does and how it is used  Renal cell carcinoma (RCC) is the most common form of kidney cancer representing approximately 90% of cases. Approximately 30% of patients present with metastatic disease, 25% with locally advanced disease, and 45% with localized disease.  Treatment of RCC is dependent on tumor type and disease stage. Surgical resection is currently the only effective treatment for localized RCC. Primary treatment involves removal of the entire kidney, adrenal gland, and some surrounding fatty tissue and nearby lymph nodes. Smaller renal cell tumors are treated by performing a partial nephrectomy. Radiation therapy may be used to treat RCC either prior to or following surgical procedures. It may be used as the main form of treatment for those patients too fragile to undergo surgery, although it is not routinely recommended due to poor response rates. Treatment of metastatic RCC involves the use of immunotherapy with interleukin-2 and interferon-alpha, alone or in combination with chemotherapy.  Sorafenib is a multiple kinase inhibitor indicated for the treatment of advanced (metastatic) RCC. Sorafenib works by inhibiting cancer cell proliferation by blocking angiogenesis (the formation of new blood vessels) in tumors.  Progression free survival (PFS) is currently used as the predictor of clinical benefit in cancer clinical trials. In one clinical study, the median PFS for patients randomized to sorafenib was 167 days compared to 84 days in those given placebo. Another study showed PFS to be 163 days in patients treated with sorafenib and 41 days in patients treated with placebo.  Sorafenib is also used to treat hepatocellular carcinoma (HCC).  Hepatocellular carcinoma (HCC) is the most common form of liver cancer representing approximately 90% of cases.  No standard medication options exist for HCC and treatment is limited to surgical resection and liver transplantation. Only about 15% of patients receive benefit from these invasive procedures.  Clinical studies such as the Sorafenib HCC Assessment Randomized Protocol (SHARP) revealed significant improvement in overall survival (OS) versus placebo. The median OS for patients randomized to sorafenib was 10.7 months versus 7.9 months in those given placebo. It also significantly prolonged time to progression (TTP) versus placebo. The median TTP for sorafenib was 5.5 months compared to 2.8 months in those given placebo.  According to the National Comprehensive Cancer Network (NCCN) guidelines for soft tissue sarcomas, Nexavar can also be used for gastrointestinal stromal tumors (GIST) when disease progression has been experienced with imatinib (Gleevec®) and sunitinib (Sutent®)  Gastrointestinal stromal tumors are KIT-expressing and KIT (tyrosine kinase receptor - CD117)-signaling driven tumors.  Gastrointestinal stromal tumors (GISTs) are fairly rare tumors of the GI tract. These tumors can start anywhere in the GI tract, but they occur most often in the stomach (about 60%) or the small intestine (about 30%). The rest are found in the esophagus, large intestine (colon and rectum), and anus  Gastrointestinal stromal tumors (GISTs) are not common, but the exact number of people diagnosed with these tumors each year is not known. Up until the late 1990s, not much was known about these tumors, so many of them ended up being classified as other kinds of GI cancers. Current estimates for the total number of GIST cases each year in the United States range from about 4,000 to about 5,000.  The recommended dose of sorafenib is 400 mg as two 200 mg tablets twice daily. If the dose needs to be reduced or discontinued due to side effects, it should be restarted at 400 mg once daily. If side effects continue, a single dose of 400 mg every other day should be given. Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs. The most common adverse events reported with sorafenib are hand- foot skin reaction, diarrhea, rash/desquamation, fatigue, alopecia, and nausea/vomiting.  Sorafenib is currently being investigated for the treatment of various other forms of cancer including metastatic colorectal and breast cancers, advanced soft tissue sarcomas, and unresectable Stage III or IV melanoma.

What it costs Dosing AWP per 200 mg tablet AWP per day Cost per month (30 days) 400 mg (2 tablets) twice daily $80.94 $323.76 $9712.80 without food

Rationale for prior authorization To reduce exposure to cost associated with the treatment of other cancers for which the effectiveness of sorafenib is not known.

Benefit design  Coverage is determined through prior authorization for every claim. AND  Coverage is provided for a quantity of tablets sufficient to treat advanced renal cell carcinoma, hepatocellular carcinoma and GIST.

Prior authorization criteria Coverage for sorafenib (Nexavar®) is provided in accord with the following: Medco Health Solutions, Inc. Nexavar Used Under License February 2012

 Treatment of advanced renal cell carcinoma. OR  Treatment of hepatocellular carcinoma. OR  Treatment of gastrointestinal stromal tumor (GIST) after disease progression with imatinib and sunitinib.

Coverage duration: 6 months. Coverage is renewable for up to 3 months in the absence of disease progression.

Quantity duration limit: Coverage is provided at a dose of up to 800 mg per day. Coverage for an additional quantity is not provided.

References  Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II Study in Patients with Advanced Hepatocellular Carcinoma. J Clin Oncol 2006; 24(26):4293-4300.  Bayer Scientific Magazine Research. Nexavar Shown to Significantly Extend Survival for Patients with Advanced Liver Cancer. Available at http://www.research.bayer.com/en/News_Detail.aspx?id=7766 Accessed on October 12, 2007.  Gastrointestinal stromal tumor. Available at http://www.cancer.org/Cancer/GastrointestinalStromalTumorGIST/DetailedGuide/gastrointestinal-stromal-tumor-what- is-gist Accessed January 2012.  Kindler H, et al. Sorafenib in patients with imatinib and sunitinib-resistant gastrointestinal stromal tumors: Final results of a University of Chicago Phase II Consortium trial. Journal of Clinical Oncology, 2011 ASCO Meeting Proceedings (post-meeting edition). Vol 29, No 15_suppl (May 20 Supplement), 2011:10009  Llovet J, Ricci S, Mazzaferro V, et al. Sorafenib Improves Survival in Advanced Hepatocellular Carcinoma (HCC): Results of a Phase III Randomized Placebo-Controlled Trial (SHARP trial). J Clin Oncol 2007; 25(18S). Available at http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010 VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abstractID=32716. Accessed on October 16, 2007.  National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Kidney Cancer. Version 2.2009. Available at http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf Accessed last on April 2, 2009.  National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Soft Tissue Sarcoma. Version 2.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/sarcoma.pdf Accessed September 2011.  Nexavar (sorafenib). Prescribing information. Bayer Healthcare. Wayne, NJ: October 2010.  Reichardt M, et al. Sorafenib fourth-line treatment in imatinib-, sunitinib-, and nilotinib-resistant metastatic GIST: A retrospective analysis. J Clin Oncol, 2009 ASCO Meeting Proceedings (post-meeting edition). Vol 27, No 15S (May 20 Supplement), 2009:10564  Stamatakos M, et al. Gastrointestinal stromal tumor. World J Surg Oncol. 2009; 7: 61.

Medco Health Solutions, Inc. Nexavar Used Under License February 2012