Prior Authorization Review Panel MCO Policy Submission

Transcription

1 Prior Authorization Review Panel MCO Policy Submission A separate copy of this form must accompany each policy submitted for review. Policies submitted without this form will not be considered for review. Plan: Aetna Better Health Submission Date: 09/01/2018 Policy Number: 0929 Policy Name: Lutetium Lu 177 Dotatate (Lutathera) Effective Date: Revision Date: 05/31/2018 Type of Submission Check all that apply: New Policy Revised Policy* Annual Review No Revisions *All revisions to the policy must be highlighted using track changes throughout the document. Please provide any clarifying information for the policy below: CPB 929 Lutetium Lu 177 Dotatate (Lutathera) This CPB has been revised to add that Lutathera is considered medically necessary for the management of locoregional advanced and/or metastatic bronchopulmonary/thymus tumors if somatostatin receptor positive imaging and progression on octreotide/lanreotide in (i) low grade (typical) disease and clinically significant tumor burden or evidence of disease progression or (ii) intermediate grade (atypical) disease. Name of Authorized Individual (Please type or print): Signature of Authorized Individual: Dr. Bernard Lewin, M.D. Revised 05/31/2018

2 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 1 of 9 ( Lutetium Lu 177 Dotatate (Lutathera) Number: 0929 Please see amendment for Pennsylvania Medicaid at the end of this CPB. Policy Aetna considers lutetium Lu 177 dotatate (Lutathera) medically necessary for members with the following indication: Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. Management of locoregional advanced and/or metastatic bronchopulmonary/thymus tumors if somatostatin receptor positive imaging and progression on octreotide/lanreotide with the following: Low grade (typical) disease and clinically significant tumor burden or evidence of disease progression; or Intermediate grade (atypical) disease Policy History Last Review 05/31/2018 Effective: 05/05/2018 Next Review: 10/25/2019 Review History Definitions Additional Information Clinical Policy Bulletin Notes

3 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 2 of 9 Aetna considers lutetium Lu 177 dotatate experimental and investigational for all other indications. Background On January 26, 2018, The FDA approved lutetium Lu 177 dotatate (Lutathera) in adult patients for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This is the first time a radioactive drug, or radiopharmaceutical, has been approved for the treatment of GEP-NETs. Lutathera was approved under priority review and received Orphan Drug designation. GEP- NETs can be present in the pancreas and in different parts of the gastrointestinal tract such as the stomach, intestines, colon and rectum. It is estimated that approximately one out of 27,000 people are diagnosed with GEP-NETs per year. Lutetium Lu 177 dotatate is a radioactive drug that binds to a part of a cell called a somatostatin receptor, which may be present on certain tumors. After binding to the receptor, the drug enters the cell allowing radiation to cause damage to the tumor cells. The approval of lutetium Lu 177 dotatate was supported by two studies. In the NETTER-1 trial, Strosberg et al (2017) stated patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of

4 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 3 of 9 lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptorpositive midgut neuroendocrine tumors. The study randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu- Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide longacting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu- Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a pre-specified interim analysis of overall survival was conducted and is reported here. At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. The

5 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 4 of 9 authors concluded that treatment with 177Lu- Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. The second study, ERASMUS, was based on data patients with somatostatin receptor-positive tumors, including GEP-NETS, who received lutetium Lu 177 dotatate at a single site in the Netherlands. A total of 1214 patients received lutetium Lu 177 dotatate, of which 601 (50%) were assessed per RECIST criteria. Of the 601 patients evaluated by investigators using RECIST criteria, 360 (60%) had gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lutetium Lu 177 dotatate 7.4 GBq (200 mci) was administered every 6 to 13 weeks for up to 4 doses concurrently with the recommended amino acid solution. The major efficacy outcome was investigator-assessed ORR. The median age in the efficacy subset was 61 years (25 to 88 years), 52% were male, 61% had a baseline Karnofsky performance status 90 (60 to 100), 60% had progressed within 12 months of treatment, and 15% had received prior chemotherapy. Fifty five percent (55%) of patients received a concomitant somatostatin analog. The median dose of lutetium Lu 177 dotatate was 29.6 GBq (800 mci). Baseline tumor assessments were obtained in 39% of patients. The investigator assessed ORR was 16% (95% CI

6 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 5 of 9 13, 20) in the 360 patients with GEP-NETs. Three complete responses were observed (< 1%). Median DoR in the 58 responding patients was 35 months (95% CI: 17, 38). Common side effects include low levels of white blood cells (lymphopenia), high levels of enzymes in certain organs (increased GGT, AST and/or ALT), vomiting, nausea, high levels of blood sugar (hyperglycemia) and low levels of potassium in the blood (hypokalemia). Serious side effects include low levels of blood cells (myelosuppression), development of certain blood or bone marrow cancers (secondary myelodysplastic syndrome and leukemia), kidney damage (renal toxicity), liver damage (hepatotoxicity), abnormal levels of hormones in the body (neuroendocrine hormonal crises) and infertility. Lutetium Lu 177 dotatate can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Patients taking lutetium Lu 177 dotatate are exposed to radiation. Exposure of other patients, medical personnel, and household members should be limited in accordance with radiation safety practices. The NCCN Compendia provides the following recommendations for GEP-NETs: In neuroendocrine tumors of the gastrointestinal tract, lung and thymus (Carcinoid Tumors), the NCCN Compendia recommends considering lutetium for management of progressive locoregional advanced disease of the gastrointestinal tract and/or distant metastases if somatostatin receptor positive imaging and progression on

7 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 6 of 9 octreotide/lanreotide. This is a NCCN Category 1 recommendation for mid-gut tumors and 2A for all others. In neuroendocrine tumors of the pancreas, there is a NCCN Category 2A recommendation for lutetium for the management of progressive locoregional advanced disease and/or distant metastatic disease if somatostatin receptor positive imaging and progression on octreotide/lanreotide. In neuroendocrine and Adrenal Tumors classified as pheochromocytoma/paraganglioma, there is a NCCN Category 2A recommendation for lutetium for primary treatment for locally unresectable disease or distant metastases if somatostatin receptor positive imaging. Recently, the NCCN Compendia has also been updated to add a 2A recommendation for lutetium for the management of locoregional advanced bronchopulmonary/thymic disease and/or distant metastases if somatostatin receptor positive imaging and progression on octreotide/lanreotide with the following: clinically significant tumor burden and low grade (typical) histology or evidence of progression; or intermediate grade (atypical) histology Appendix Lutathera Injection is available as 370 MBq/mL (10 mci/ml) of lutetium Lu 177 dotatate in a sterile, preservative-free and clear, colorless to slightly yellow solution for intravenous use supplied in a colorless Type I glass 30 ml singledose vial containing 7.4 GBq (200 mci) ± 10% of lutetium Lu 177 dotatate at the time of injection.

8 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 7 of 9 The FDA-approved dosing is 7.4 GBq (200 mci) every 8 weeks for a total of 4 doses. Administer pre- and concomitant medications and administer Lutathera as recommended. CPT Codes / HCPCS Codes / ICD-10 Codes Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+": Code Code Description HCPCS codes covered if selection criteria are met: Lutathera (lutetium Lu 177 dotatate) - no specific code : ICD-10 codes covered if selection criteria are met: C7A.00 - Malignant neuroendocrine tumors C7A.8 The above policy is based on the following references: 1. U.S. Food and Drug Administration (FDA). FDA approves new treatment for certain digestive tract cancers. Silver Spring, MD: FDA; January 26, Available at: Accessed February 13, Advanced Accelerator Applications USA, Inc. Lutathera (lutetium Lu 177 dotatate) injection for intravenous use. Prescribing Information. Millburn, NJ: Advanced Accelerator Applications USA, Inc.; January Strosberg J, El-Haddad G, Wolin E, et al.; NETTER-1 Trial Investigators. Phase 3 Trial of (177)Lu-Dotatate for Midgut

9 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 8 of 9 Neuroendocrine Tumors. N Engl J Med. 2017;376(2): National Comprehensive Cancer Network (NCCN). Lutathera. NCCN Drugs & Biologics Compendium. Fort Washington, PA: NCCN; 2018.

10 Lutetium Lu 177 Dotatate (Lutathera) - Medical Clinical Policy Bulletins Aetna Page 9 of 9 Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change. Copyright Aetna Inc.

11 AETNA BETTER HEALTH OF PENNSYLVANIA Amendment to Aetna Clinical Policy Bulletin Number: 0929 Lutetium Lu 177 Dotatate (Lutathera) For the Pennsylvania Medical Assistance Plan, the use of Lutathera will be considered on a case by case basis for use in the management of neuroendocrine tumors of the lung and thymus and for the treatment of pheochromocytoma/paraganglioma. Review will be based upon NCCN guidelines in effect at the time of review. revised 5/31/2018