Cigna National Formulary Coverage Policy

Prior Authorization Policy Oncology – Tasigna® (nilotinib capsules)

Table of Contents Product Identifier(s)

National Formulary Medical Necessity ...... 1 03053 Conditions Not Covered...... 2 Background ...... 2 References ...... 3 Revision History ...... 3

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

National Formulary Medical Necessity

Cigna covers nilotinib (Tasigna®) as medically necessary when the following criteria are met for FDA Indications or Other Uses with Supportive Evidence:

Prior Authorization is recommended for prescription benefit coverage of Tasigna. All approvals are provided for the duration noted below.

FDA Indication(s)

1. Chronic Myeloid Leukemia. Approve for 3 years if the individual has Philadelphia chromosome-positive chronic myeloid leukemia.

Other Uses with Supportive Evidence

2. Acute Lymphoblastic Leukemia. Approve for 3 years if the individual meets the following (A, B, and C): A) Individual is ≥ 18 years of age; AND B) Individual has Philadelphia chromosome-positive acute lymphoblastic leukemia; AND

Page 1 of 3 Cigna National Formulary Coverage Policy: PA Oncology – Tasigna C) Individual has tried at least one other tyrosine kinase inhibitor for Philadelphia chromosome-positive acute lymphoblastic leukemia. Note: Examples include Gleevec (imatinib tablets) and Sprycel (dasatinib tablets).

3. Gastrointestinal Stromal Tumor. Approve for 3 years if the individual meets the following (A and B): A) Individual is ≥ 18 years of age; AND B) Individual has tried each of the following (i, ii, iii, and iv): i. Imatinib or Avyakit (avapritinib tablets); AND ii. Sutent (sunitinib capsules); AND iii. Stivarga (regorafinib tablets); AND iv. Qinlock (ripretinib tablets).

4. Myeloid/Lymphoid Neoplasms with Eosinophilia. Approve for 3 years if the individual meets the following (A and B): A) Individual is ≥ 18 years of age; AND B) The tumor has an ABL1 rearrangement.

Conditions Not Covered

Nilotinib capsules (Tasigna®) is considered experimental, investigational or unproven for ANY other use.

Background

Overview Tasigna, a tyrosine kinase inhibitor (TKI), is indicated for the following uses:1 • Chronic myeloid leukemia (CML), chronic phase, newly diagnosed and Philadelphia chromosome positive (Ph+), in adult and pediatric patients ≥ 1 year of age. • CML, Ph+, chronic phase and accelerated phase, in adults with resistance to or intolerance to prior therapy that included imatinib. • CML, Ph+, chronic phase, in pediatric patients ≥ 1 year of age with resistance or intolerance to prior TKI therapy.

Guidelines Tasigna is addressed in a few guidelines from National Comprehensive Cancer Network (NCCN): • Acute Lymphoblastic Leukemia (ALL): The NCCN guidelines for ALL (version 1.2021 – April 6, 2021) [adults] recommend Tasigna as an option for patients with relapsed or refractory ALL (category 2A).2 • CML: NCCN guidelines for CML (version 3.2021 – January 13, 2021) state that for patients with chronic phase CML with a low-risk score, the primary treatment recommended includes a first-generation TKI (imatinib [brand or generic]), or a second-generation TKI (Bosulif® [bosutinib tablets], Sprycel® [dasatinib tablets], or Tasigna [all category 1]).3 For patients with chronic phase CML with an intermediate- or high-risk score, a second-generation TKI is preferred (Bosulif [category 1], Sprycel [category 1], or Tasigna [category 1]). A first-generation TKI (imatinib [brand or generic]) is an alternative (category 2A). Iclusig® (ponatanib tablets) is an option for patients with a T315I mutation and/or chronic phase CML with resistance or intolerance to at least two prior TKIs or for patients with accelerated-phase CML or blast-phase CML for whom no other TKI is indicated (category 2A). • Gastrointestinal Stromal Tumor (GIST): According to the NCCN GIST guidelines (version 1.2021 – October 30, 2020), Tasigna is recommended as useful in certain circumstances after failure on approved therapies (category 2A).4 Imatinib is a preferred regimen for first-line therapy (category 1). Ayvakit® (avapritinib tablets) is also a preferred regimen (category 2A) for GIST with platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutations, including the PDGFRA D842V mutation. Sutent® (sunitinib capsules) is a preferred regimen (category 1) for second-line therapy (progressive disease after imatinib). Stivarga® (regorafenib tablets) is a preferred regimen (category 1) for third-line therapy (progressive disease after imatinib and Sutent). Qinlock™ (ripretinib tablets) is a preferred regimen (category 1) for fourth-line therapy (progressive disease after imatinib, Sutent, and Stivarga). Besides Tasgina, other additional options after failure on approved therapies that are useful in certain

Page 2 of 3 Cigna National Formulary Coverage Policy: PA Oncology – Tasigna circumstances include Ayvakit, Sprycel (for patients with the PDGFRA D842V mutation), Nexavar® (sorafenib tablets), Votrient® (pazopanib tablets), and everolimus plus TKIs (all category 2A). • Myeloid/Lymphoid Neoplasms with Eosinophilia: The NCCN guidelines for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes (version 3.2021 – August 21, 2020) note that Tasigna is a TKI with activity against ABL1 rearrangements (category 2A) and it may have a role for use in patients with this condition.5

References

1. Tasigna® capsules [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals, Inc.; December 2020. 2. The NCCN Acute Lymphoblastic Leukemia Clinical Practice Guidelines in Oncology (version 1.2021 – April 6, 2021). © 2021 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed on April 9, 2021. 3. The NCCN Chronic Myeloid Leukemia Clinical Practice Guidelines in Oncology (version 3.2021 – January 13, 2021). © 2021 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed on April 9, 2021. 4. The NCCN Gastrointestinal Stromal Tumors Guidelines in Oncology (Version 1.2021 – October 30, 2020). © 2021 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed on 06/14/2021. 5. The NCCN Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes Clinical Practice Guidelines in Oncology (version 3.2021 – August 21, 2020). © 2020 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed on April 1, 2021.

Revision History

Type of Summary of Changes Approval Date Revision Annual The following criteria changes were made: 04/14/2021 Revision 1. Acute Lymphoblastic Leukemia: The condition of approval was changed to move the notation that the disease is “Philadelphia chromosome-positive” to the criteria section. The requirement that the patient is ≥ 18 years of age was added. 2. Chronic Myeloid Leukemia: The condition of approval was changed to move the notation that the disease is “Philadelphia chromosome-positive” to the criteria section. 3. Gastrointestinal Stromal Tumor: The requirement was removed that the patient has tried Gleevec (imatinib tablets), Sutent (sunitinib capsules), and Stivarga (regorafenib tablets). The requirements that the patient is ≥ 18 years of age and that the patient has tried at least three other medications were added. The examples of medications are provided in a Note. 4. Myeloid/Lymphoid Neoplasms with Eosinophilia: This was added as a new condition of approval. Selected Gastrointestinal Stromal Tumor (GIST): Patient has tried at least three other 06/23/2021 Revision medications was reworded to “Patient has tried each of the following, imatinib or Avyakit, Sutent (sunitinib capsules); Stivarga (regorafinib tablets); AND Qinlock (ripretinib tablets) The note of examples of medications was removed.

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Page 3 of 3 Cigna National Formulary Coverage Policy: PA Oncology – Tasigna