Description Sorafenib (Nexavar) is an oral medication used to treat certain types of cancer. It works by blocking the growth of cancer cells.

Transcription

1 Medication Policy Manual Policy No: dru134 Topic: Nexavar, sorafenib Date of Origin: March 10, 2006 Committee Approval Date: November 13, 2014 Next Review Date: November 2015 Effective Date: December 1, 2014 IMPORTANT REMINDER This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status. Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care. Description Sorafenib (Nexavar) is an oral medication used to treat certain types of cancer. It works by blocking the growth of cancer cells. dru Page 1 of 10

2 Policy/Criteria I. Most contracts require prior authorization approval of sorafenib (Nexavar) prior to coverage. Sorafenib (Nexavar) may be considered medically necessary in patients when both criteria A and B below are met. A. Documentation of one of the following diagnoses is provided: 1. Hepatocellular carcinoma. OR 2. Renal cell carcinoma when prior therapy with sunitinib (Sutent) has been ineffective, is contraindicated, or was not tolerated. OR 3. Locally recurrent or metastatic differentiated (papillary or follicular) thyroid carcinoma refractory to radioactive iodine treatment. AND B. Sorafenib (Nexavar) is dispensed from a pharmacy that has demonstrated the ability to provide the clinical support services outlined in Appendix 1. II. III. Administration, Quantity Limitations, and Authorization Period A. RegenceRx considers sorafenib (Nexavar) to be a self-administered medication. B. When prior authorization is approved, up to 120 sorafenib (Nexavar) 200 mg tablets may be authorized per month. Quantities exceeding 120 tablets per month are considered not medically necessary. C. Authorization may be reviewed at least annually to confirm that current medical necessity criteria are met and that the medication is effective. Sorafenib (Nexavar) is considered investigational when used for all other conditions, including but not limited to: A. Acute myeloid leukemia B. Breast cancer C. Colorectal cancer D. Malignant melanoma E. Non-small cell lung cancer F. Osteosarcoma G. Ovarian cancer H. Pancreatic cancer I. Soft tissue sarcoma J. Medullary or anaplastic thyroid carcinoma K. Urothelial cancer of the bladder or upper urinary tract dru Page 2 of 10

3 Position Statement Summary - Sorafenib (Nexavar), an orally administered tyrosine kinase inhibitor, may be covered for certain cancers where it has been shown to be safe and effective, including hepatocellular carcinoma, renal cell carcinoma, and thyroid carcinoma. - Sorafenib (Nexavar) has demonstrated improved overall survival when used in patients with unresectable hepatocellular carcinoma. - Although there is no useful evidence that any one agent is more effective than another, when the use of a tyrosine kinase inhibitor is indicated, sunitinib (Sutent) is the best value for patients with advanced or metastatic renal cell carcinoma. * In patients with advanced renal cell carcinoma, sorafenib (Nexavar) improved progression-free survival, an endpoint that uses x-rays to measure the size of tumors. * There is currently no high quality data showing that sorafenib (Nexavar) improves overall survival in patients with advanced renal cell carcinoma. - Sorafenib (Nexavar) has demonstrated improved progression-free survival when used in patients with locally recurrent or metastatic thyroid carcinoma following radioactive iodine treatment. - Sorafenib (Nexavar) may be covered at the doses at which it has been shown to be effective (up to 800 mg per day). Clinical Efficacy HEPATOCELLULAR CARCINOMA - There is high confidence in the evidence that sorafenib (Nexavar) improves overall survival in patients with advanced stages of hepatocellular carcinoma. - In a large clinical trial, median overall survival improved from about 8 months to about 11 months in patients who were taking sorafenib (Nexavar) rather than placebo (receiving best supportive care). [1] - In another clinical trial of patients with advanced hepatocellular carcinoma who had not received prior therapy, median overall survival was 6.5 months (95% CI: 5.6 to 7.6) vs 4.2 months (95% CI: 3.8 to 5.5) in the sorafenib (Nexavar) and placebo groups, respectively. [2] - The National Comprehensive Cancer Network (NCCN) guidelines recommend sorafenib (Nexavar) as a single agent treatment option for patients with unresectable or metastatic hepatocellular carcinoma. [3] dru Page 3 of 10

4 RENAL CELL CARCINOMA - A large phase III trial compared the efficacy of sorafenib (Nexavar) vs placebo (best supportive care) in 903 patients with advanced (metastatic and/or unresectable) renal cell carcinoma that was resistant to standard therapy. * An intermediate analysis of progression free survival, showed a statistically significant difference in favor of the sorafenib (Nexavar) group vs the placebo group (5.5 months versus 2.8 months, respectively). [4] * However, final overall survival was not statistically different between patients receiving sorafenib (Nexavar) vs patients receiving placebo (17.8 months and 15.2 months, respectively; p = 0.146). [5] - In another study of 723 patients with renal cell carcinoma who had progressed on one prior therapy, median progression free survival was 4.7 months with sorafenib (Nexavar) vs 6.7 months with axitinib (Inlyta) (95% CI: 0.54 to 0.81; p < ). [6] - Current NCCN guidelines recommend sorafenib (Nexavar) as a treatment option for patients with renal cell carcinoma. For patients with predominantly clear cell histology, sorafenib (Nexavar) is recommended as first-line therapy for select patients (Category 2A) and as second-line therapy following cytokine therapy (Category 1) or another tyrosine kinase inhibitor (Category 2A). Sorafenib (Nexavar) is also recommended as a first-line treatment option for patients with non-clear cell histology (Category 2A). [7] DIFFERENTIATED THYROID CARCINOMA - Sorafenib (Nexavar) was evaluated in a randomized, double-blind, placebo-controlled trial in 417 patients with locally recurrent or metastatic thyroid carcinoma refractive to radioactive iodine treatment. [8,9] * A statistically significant improvement in progression-free survival was reported for patients treated with sorafenib (Nexavar) versus those treated with placebo (median 10.8 months vs 5.8 months; hazard ratio 0.59; 95% CI: 0.46, 0.76; p < 0.001). * There was no statistically significant difference in overall survival between the two treatment groups. - NCCN guidelines recommend sorafenib (Nexavar) as a treatment option for patients with thyroid carcinoma. For patients with follicular and papillary thyroid carcinoma, sorafenib (Nexavar) is recommended following lack of response to radioactive iodine treatment (Category 2A). Sorafenib (Nexavar) is also recommended in patients with medullary thyroid carcinoma and Hürthle cell carcinoma (Category 2A); however, these patients were not evaluated in the pivotal clinical trial and, therefore, the safety and efficacy of sorafenib (Nexavar) in these patients cannot be confirmed. [10] dru Page 4 of 10

5 OTHER CONDITIONS Sorafenib (Nexavar) is being studied in several other conditions; however, due to lack of positive data, or lack of data from large, high quality randomized controlled trials, these conditions are considered investigational. - In a population of elderly patients with acute myeloid leukemia, the addition of sorafenib (Nexavar) to standard induction and consolidation therapy did not result in significant improvement of event-free survival or overall survival, but did increase toxicity. [11] - The addition of sorafenib (Nexavar) to capecitabine (Xeloda) improved progression-free survival vs placebo (median 6.4 and 4.1 months, respectively) in a phase II trial evaluating patients with locally advanced or metastatic HER-2 negative breast cancer. [12] - Partial response was slightly improved when sorafenib (Nexavar) was added to cetuximab (Erbitux) in 35 patients with metastatic colorectal cancer; although, the difference was not statistically significant. [13] In another trial, overall survival was not improved for patients with metastatic colorectal cancer treated with sorafenib (Nexavar) in addition to oxaliplatin, levo-leucovorin, and fluorouracil compared to patients treated with oxaliplatin, levo-leucovorin, and fluorouracil alone. [14] - Sorafenib (Nexavar) in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable/advanced melanoma failed to improve progression-free survival or overall survival. [15] - A large phase III trial evaluating sorafenib (Nexavar) in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable non-small cell lung cancer was stopped early when no overall survival benefit was demonstrated in an interim analysis. [16] Another trial evaluating sorafenib (Nexavar) in combination with cisplatin and gemcitabine in this population also failed to meet its primary endpoint of improved overall survival. [17] - Progression-free survival at four months was 46% (95% CI: 28%, 63%) in an uncontrolled trial evaluating sorafenib (Nexavar) as monotherapy in 35 patients with relapsed and unresectable osteosarcoma. [18] Due to limited treatment options in this setting, sorafenib (Nexavar) is listed in the NCCN guidelines as second-line therapy. [19] - There was no significant difference in progression-free survival between sorafenib (Nexavar) and placebo (median 12.7 vs 15.7 months; hazard ratio 1.09; 95% CI: 0.72, 1.63) when evaluated as maintenance therapy in patients with ovarian cancer in complete remission. [20] - Neither sorafenib (Nexavar) alone, nor sorafenib in combination with gemcitabine produced an objective response in patients with metastatic pancreatic cancer. [21] Results from a phase II study demonstrated that sorafenib (Nexavar) does not significantly enhance the activity of chemotherapy in advanced pancreatic cancer. [22] dru Page 5 of 10

6 - At 12 weeks, 8 patients (31%) with advanced soft tissue sarcoma had not progressed after treatment with sorafenib. [23] Several other small, preliminary studies have shown sorafenib to be active as salvage therapy in soft tissue sarcoma; therefore, it is listed in the NCCN guidelines (category 2A). [24] - A randomized, double-blind, phase II study failed to show improvement in progressionfree survival when sorafenib (Nexavar) was added to gemcitabine and cisplatin for locally advanced or metastatic urothelial cancer. [25] RegenceRx performs independent analyses of oncology medications. The RegenceRx analysis and coverage policy may differ from NCCN guidelines. Safety [8] - Alopecia, diarrhea, hemorrhage, hypertension, and skin reactions were the most common adverse effects reported with sorafenib. - Skin reactions included rash, desquamation, hand-foot skin reaction, alopecia, and pruritus. - Dose reduction or interruption of therapy may be necessary for severe reactions. Administration and dosing [8] - The usual dose of sorafenib is two 200-mg capsules (400 mg) orally twice a day. - Dose adjustments are necessary when skin toxicity occurs. * Reduction of dose is based on grade of skin toxicity. * Initial dose decrease should be 400 mg once per day. If additional reduction is necessary, decrease to 400 mg every other day. Pharmacy Support Services - The treatment of cancers with targeted oncology medications is unique and complex. The increased level of care provided by clinical pharmacists and experienced nurses may improve the chances of treatment success and lower overall treatment costs. * Oral cancer medications are often associated with troublesome side effects that may affect adherence to treatment regimens and decrease clinical success. Clinical pharmacists and nurses can provide patient education to help patients recognize and manage adverse effects. * Oral cancer medications are often discontinued because of disease progression or adverse effects. The ability of pharmacies to dispense smaller quantities of medication can reduce waste and patient out-of-pocket costs. dru Page 6 of 10

7 * Clinical oncology pharmacy support services may also: * Provide patient education concerning treatment frequency and duration. * Proactively provide regular patient contact to monitor for and encourage adherence. * Notify providers when patients receive medications. * Work with prescribing physicians to identify tolerability issues which may require discontinuation of therapy. * Identify and recommend the need for additional clinical interventions (e.g. dosage adjustments due to side effects or drug-drug interactions). * Identify and assist in managing other cancer-related medical problems (e.g. control of pain or nausea). dru Page 7 of 10

8 Appendix 1: Clinical Pharmacy Support Services Necessary for Dispensing Sorafenib to RegenceRx Members Implement a cycle management program that supports split-fill dosing of self-administered oral oncology medications. These medications are considered Specialty medications and are used to treat complex medical conditions requiring the additional education and support of a healthcare professional. Provide and manage split-fills of oral oncology medications to reduce the potential for waste while ensuring therapy is not unnecessarily interrupted. A member s first fill is for a 16-day supply, followed by a 14-day supply as approved. Demonstrate the ability in systems for both tracking and billing prorated copayments/coinsurance. Instruct patients at the time of each dispensing that their therapy is to continue as instructed by their physician and that regular refills of their medication will be necessary to prevent therapy interruption. Provide urgent dispensing for members to ensure that therapy is not unnecessarily interrupted. Contact members between days 10 to 12 of each month and again on day 20 of each month to monitor patients for adverse events and adherence with the goal of improving quality of care by minimizing the impact of side effects, improving outcomes, and reducing hospital admissions. Provide a comprehensive Patient Adherence Report 20 days after the start of oral chemotherapy that details dose changes, side effects, and interventions. Coordinate communication between patients and providers regarding ongoing tolerability and adherence issues with oral chemotherapy through the use of regularly scheduled follow up telephone consultations and the use of a systematic screening tool to identify and assist patients in the management of adverse effects. Provide a dedicated team of clinical pharmacists for RegenceRx membership. Provide 24 hours per day, 7 days per week availability of clinical support staff for members. Provide documentation of current ACHC and URAC accreditation. Provide reporting to RegenceRx at least quarterly to describe the following metrics: - Number of patients enrolled in oral oncology medication cycle management program. - Adherence data on patients enrolled. Note: RegenceRx reserves the right to establish whether the above conditions have been met and may revoke pharmacy approval status at any time. dru Page 8 of 10

9 Cross References Afinitor, everolimus, RegenceRx Medication Policy Manual, Policy No. dru178 Avastin, bevacizumab, RegenceRx Medication Policy Manual, Policy No. dru215 Inlyta, axitinib, RegenceRx Medication Policy Manual, Policy No. dru273 Sutent, sunitinib, RegenceRx Medication Policy Manual, Policy No. dru128 Votrient, pazopanib, RegenceRx Medication Policy Manual, Policy No. dru199 Codes Number Description HCPCS J8999 Oral chemotherapeutic drug, not otherwise classified ICD Malignant neoplasm of the liver, primary ICD Malignant neoplasm of the liver, not specified as primary or secondary ICD Malignant neoplasm of the kidney except pelvis ICD Malignant neoplasm of the renal pelvis References 1. Llovet, JM, Ricci, S, Mazzaferro, V, et al. Sorafenib in advanced hepatocellular carcinoma. United States, p Cheng, AL, Kang, YK, Chen, Z, et al. Efficacy and safety of sorafenib in patients in the Asia- Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. England, p NCCN Clinical Practice Guidelines in Oncology TM. Hepatobiliary Cancers v [cited 10/24/2014]; Available from: 4. Escudier, B, Eisen, T, Stadler, WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. United States, p Escudier, B, Eisen, T, Stadler, WM, et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. United States, p Rini, BI, Escudier, B, Tomczak, P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. England, p NCCN Clinical Practice Guideline in Oncology TM. Kidney Cancer v [cited 10/21/2014]; Available from: 8. Nexavar [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 11/ Brose, MS, Nutting, CM, Jarzab, B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet Jul 26;384(9940): PMID: NCCN Clinical Practice Guidelines in Oncology TM. Thyroid Carcinoma v [cited 10/24/2014]; Available from: Serve, H, Krug, U, Wagner, R, et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. United States, p dru Page 9 of 10

10 12. Baselga, J, Segalla, JG, Roche, H, et al. Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. United States, p Galal, KM, Khaled, Z, Mourad, AM. Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer. India, p Tabernero, J, Garcia-Carbonero, R, Cassidy, J, et al. Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) as first-line treatment of metastatic colorectal cancer: the RESPECT trial. United States, p Hauschild, A, Agarwala, SS, Trefzer, U, et al. Results of a phase III, randomized, placebocontrolled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. United States, p Scagliotti, G, Novello, S, von Pawel, J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. United States, p Paz-Ares, LG, Biesma, B, Heigener, D, et al. Phase III, randomized, double-blind, placebocontrolled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. United States, p Grignani, G, Palmerini, E, Dileo, P, et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. England, p NCCN Clinical Practice Guidelines in Oncology TM. Bone Cancer v [cited 10/24/2014]; Available from: Herzog, TJ, Scambia, G, Kim, BG, et al. A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma. Gynecologic oncology Jul;130(1): PMID: El-Khoueiry, AB, Ramanathan, RK, Yang, DY, et al. A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer. Investigational new drugs Jun;30(3): PMID: Cascinu, S, Berardi, R, Sobrero, A, et al. Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver Feb;46(2): PMID: Pacey, S, Ratain, MJ, Flaherty, KT, et al. Efficacy and safety of sorafenib in a subset of patients with advanced soft tissue sarcoma from a Phase II randomized discontinuation trial. Investigational new drugs Jun;29(3): PMID: NCCN Clinical Practice Guidelines in Oncology TM. Soft Tissue Sarcoma V [cited 10/24/2014]; Available from: Krege, S, Rexer, H, vom Dorp, F, et al. Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05). BJU international Mar;113(3): PMID: dru Page 10 of 10