Independent licensees of the Blue Cross and Blue Shield Association Medication Policy Manual Policy No: dru137 Topic: Sprycel, dasatinib Date of Origin: November 17, 2006 Committee Approval Date: October 28, 2020 Next Review Date: October 2021 Effective Date: January 1, 2021 IMPORTANT REMINDER This Medication 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 medication policy is to provide a guide to coverage. Medication 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 Dasatinib (Sprycel) is an oral tyrosine kinase inhibitor used to treat certain types of cancer. It works by blocking specific proteins that the cancer cells need to grow. © 2021 Regence. All rights reserved. dru137.18 Page 1 of 9 Policy/Criteria Most contracts require pre-authorization approval of dasatinib (Sprycel) prior to coverage. I. Continuation of therapy (COT): Dasatinib (Sprycel) may be considered medically necessary for COT when criteria A and B below are met. A. The patient is established on this therapy AND one of the following situations applies (criterion 1 or 2 below): 1. Prior to current health plan membership AND the medication was covered by another health plan. Note: If the diagnosis is not listed in the coverage criteria below, written documentation of coverage must be provided, such as an approval letter or paid claim. OR 2. The medication was initiated for acute disease management, as part of an acute unscheduled, inpatient hospital admission AND there is documented clinical benefit. AND B. If the diagnosis is not listed in the coverage criteria below, documentation of clinical benefit, such as disease stability as detailed in the reauthorization criteria, is provided. Please note: Medications obtained as samples, coupons, or promotions, paying cash for a prescription (“out-of-pocket”) as an eligible patient, or any other method of obtaining medications outside of an established health plan benefit (from your insurance) does NOT necessarily establish medical necessity. Medication policy criteria apply for coverage, per the terms of the member contract with the health plan. II. New starts (treatment-naïve patients): Dasatinib (Sprycel) may be considered medically necessary when the criteria below are met: A. Documentation of one of the following conditions in Philadelphia chromosome- positive (Ph+) patients: 1. Chronic myelogenous leukemia (CML) in the chronic phase AND at least one prior tyrosine kinase inhibitor (TKI) therapy for CML has not been effective or is contraindicated (See Appendix 1). OR 2. CML in the accelerated or blast phase when treatment with imatinib is ineffective, not tolerated or contraindicated. OR 3. Acute lymphoblastic leukemia (ALL) when treatment with imatinib is ineffective, not tolerated or contraindicated. © 2021 Regence. All rights reserved. dru137.18 Page 2 of 9 III. Administration and Authorization Period A. Regence Pharmacy Services considers dasatinib (Sprycel) to be a self- administered medication. B. When pre-authorization is approved, dasatinib (Sprycel) may be authorized in doses of up to 140 mg per day until disease progression. C. Authorization may be reviewed at least annually. Clinical documentation (including, but not limited to chart notes) must be provided to confirm that current medical necessity criteria are met, and that the medication is providing clinical benefit, such as disease stability or improvement. IV. Dasatinib (Sprycel) is considered not medically necessary when used for previously untreated CML. V. Dasatinib (Sprycel) is considered investigational when used for all other conditions, including, but not limited to: A. ALL when the Philadelphia chromosome is not present (non-Ph+ ALL). B. CML when the Philadelphia chromosome is not present (non-Ph+ CML). C. Malignant melanoma. D. Multiple myeloma (MM). E. Myeloproliferative disorders (MPD). F. Non-small cell lung cancer. G. Prostate cancer. H. Solid tumors. I. Gastrointestinal stromal tumor (GIST) Position Statement - Dasatinib (Sprycel) is an orally administered tyrosine kinase inhibitor (TKI) used in the treatment of chronic myelogenous leukemia (CML) and in Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph+ ALL) that is refractory to imatinib. - Most CML and some ALL is caused by an abnormal chromosome translocation that results in the formation of the Philadelphia chromosome which starts the disease process. - TKIs work by suppressing formation of the abnormal Philadelphia chromosome. Efficacy of TKIs is measured using a genetic test that measures the level of suppression of the Philadelphia chromosome (cytogenetic response). - There are three phases of CML: chronic, accelerated, and blast. Chronic phase CML is the most common. Accelerated and blast phase CML are associated with a higher morbidity and mortality. - The intent of this policy is to cover dasatinib (Sprycel) for the indications for which it has been studied and shown to be safe and effective, as detailed in the coverage criteria, with consideration for other available treatment options. © 2021 Regence. All rights reserved. dru137.18 Page 3 of 9 - Imatinib, dasatinib (Sprycel), and nilotinib (Tasigna) have been studied and are used to treat CML in the following clinical settings: * Imatinib has been studied and is used as a first-line therapy for CML in the chronic, accelerated and blast phases. * Dasatinib (Sprycel) has been studied as a first-line therapy for CML in the chronic phase; and as a subsequent therapy for CML in the chronic, accelerated, or blast phase after resistance or intolerance to prior imatinib therapy. * Nilotinib (Tasigna) has been studied as a first-line therapy for CML in the chronic phase; and as a subsequent therapy for CML in the accelerated phase after resistance or intolerance to prior imatinib therapy. It has not been studied in CML in the blast phase. - Imatinib produces cytogenetic response (surrogate measure of efficacy) in the majority of patients with chronic phase CML and is associated with improved overall survival. - Dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif) have demonstrated improvement in surrogate markers of disease response compared to imatinib 400 mg daily. However, differences in overall survival or other clinically meaningful endpoints were not observed in comparative trials. - The efficacy of dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif) compared to an imatinib 600 mg daily is not known. - Myelosuppression, skin reactions, and hepatic impairment occur with all of the TKIs. Specific adverse events (AEs) may be more prevalent with one TKI versus another: * Higher rates of fluid retention are reported with imatinib than with other TKIs. * Dasatinib (Sprycel) may cause pulmonary AEs such as pleural effusion and pulmonary arterial hypertension. * Nilotinib (Tasigna) is associated QT prolongation. - There are currently no well-controlled studies that establish the safety and efficacy of dasatinib (Sprycel) in other types of leukemias or cancers. - Usual doses of dasatinib (Sprycel) range from 100 mg to 140 mg daily. The safety and efficacy of dasatinib (Sprycel) in doses above 140 mg daily have not been established. Regence Pharmacy Services performs independent analyses of oncology medication evidence. NCCN clinical practice guidelines assignment of a category 2a/b recommendation does not necessarily establish medically necessity. The Regence Pharmacy Services analysis and coverage policy may differ from NCCN clinical practice guidelines. © 2021 Regence. All rights reserved. dru137.18 Page 4 of 9 Summary Clinical Efficacy CHRONIC MYELOGENOUS LEUKEMIA (CML) - The quality of evidence for the TKIs [imatinib, dasatinib (Sprycel), nilotinib (Tasigna), bosutinib (Bosulif)] in CML is reliable and suggests that these medications are effective and that they improve overall survival relative to historical controls. - Imatinib was the first TKI approved for the treatment of CML and is effective in the majority of cases in the first-line setting. Complete cytogenetic response (CCyR) rates at one year range from 57 to 88% in various imatinib studies. - In the first-line treatment of CML, there is evidence that dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif) have been shown to improve surrogate markers of disease response compared to imatinib 400 mg daily. However, no difference in overall survival has been demonstrated. The effectiveness compared to imatinib 600 mg daily has not been studied. ∗ A reliable study comparing dasatinib (Sprycel) with imatinib in the first-line treatment of CML reported an 11% improvement in CCyR at one year for dasatinib (Sprycel) over imatinib (77% versus 66%, respectively). [1] However, mature 5-year overall survival was not different between groups (91% vs 90%). ∗ A reliable study comparing nilotinib (Tasigna) with imatinib in the first-line treatment of CML reported a 14% improvement in CCyR (secondary endpoint) at one year for nilotinib (Tasigna) over imatinib (79% versus 65%, respectively). [2] However, mature 5-year overall survival