TAFINLAR, Dabrafenib Mesylate Form

Dabrafenib (Tafinlar®) is a kinase inhibitor. FDA Approved Indication(s) Tafinlar is indicated: • As a single agent for the treatment of patients with unresectable or metastatic melanoma with • BRAF V600E mutation as detected by an FDA-approved test In combination with trametinib (Mekinist®): o For the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test o For the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection o For the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test o For the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options o For the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options* o For the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy Limitation(s) of use:
• Tafinlar is not indicated for treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition. • Tafinlar is not indicated for treatment of patients with wild-type BRAF solid tumors. _

• This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
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  CLINICAL POLICY Dabrafenib It is the policy of health plans affiliated with Centene Corporation® that Tafinlar is medically necessary when the following criteria are met:
  I. Initial Approval Criteria
  A. Melanoma (must meet all):

  1. Diagnosis of melanoma with BRAF V600E or V600K mutation;
  2. Disease meets one of the following (a or b): a. Unresectable, limited resectable, or metastatic; b. Presence of lymph node(s) involvement following complete resection;
  3. Prescribed by or in consultation with an oncologist;
  4. Age ≥ 18 years;
  5. Prescribed as one of the following (a or b): a. In combination with Mekinist; b. As a single agent for unresectable or metastatic disease with BRAF V600E mutation;
  6. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  7. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
     i. 300 mg per day; ii. 4 capsules per day;
     b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
     Approval duration:
     Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
     B. Non-Small Cell Lung Cancer (must meet all):
  8. Diagnosis of advanced, metastatic, or recurrent NSCLC;
  9. Prescribed by or in consultation with an oncologist;
  10. Age ≥ 18 years;
  11. Disease is positive for a BRAF V600E mutation;
  12. Prescribed in combination with Mekinist, unless the combination is not tolerated;
  13. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  14. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
      i. 300 mg per day; ii. 4 capsules per day;
      b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
      Approval duration:
      Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
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  CLINICAL POLICY Dabrafenib C. Thyroid Cancer (must meet all):

  1. Diagnosis of advanced or metastatic thyroid cancer (ATC, follicular, papillary, or Hürthle cell carcinoma);
  2. Prescribed by or in consultation with an oncologist;
  3. Age ≥ 18 years;
  4. One of the following (a or b): a. For ATC: Disease is positive for BRAF V600E mutation; b. For follicular, papillary, or Hürthle cell carcinoma: both of the following (i and ii): i. Disease is positive for a BRAF mutation; ii. Disease is not amenable to radioactive iodine therapy;
  5. For ATC requests, prescribed in combination with Mekinist;
  6. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  7. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
     i. 300 mg per day; ii. 4 capsules per day;
     b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
     Approval duration:
     Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
     D. BRAF V600E Mutation-Positive Solid Tumor (must meet all):
  8. Diagnosis of unresectable or metastatic solid tumor that is positive for a BRAF V600E mutation (see Appendix D for examples);
  9. Prescribed by or in consultation with an oncologist;
  10. Age ≥ 1 year;
  11. Request meets one of the following (a or b): a. Disease has progressed on prior treatment, and no satisfactory alternative treatment options are available;
      b. Prescribed for one of the following NCCN 2A or higher supported indications (i- vii):
      i. Ampullary adenocarcinoma, as subsequent therapy; ii. Salivary gland tumor;
      iii. Pancreatic adenocarcinoma;
      iv. One of the thyroid carcinomas, as subsequent treatment in unresectable, recurrent, persistent, or metastatic disease (a, b, or c):
      a) Papillary;
      b) Follicular;
      c) Hürthle cell;
      v. One of the following hepatobiliary cancers, as subsequent treatment in unresectable or metastatic disease (a, b, or c):
      a) Extrahepatic cholangiocarcinoma;
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  CLINICAL POLICY Dabrafenib b) Intrahepatic cholangiocarcinoma;
  c) Gallbladder cancer;
  vi. One of the following central nervous system cancers (a-f):
  a) Adult low-grade (World Health Organization [WHO] grade 1) gliomas;
  b) Recurrent adult isocitrate dehydrogenase (IDH) mutant oligodendroglioma (1p19q codeleted, WHO grade 2 or 3); c) Recurrent adult IDH mutant astrocytoma (WHO grade 2, 3, or 4);
  d) Recurrent adult glioblastoma;
  e) Brain metastases;
  f) Pediatric diffuse high-grade gliomas, as adjuvant treatment (except for diffuse midline glioma, H3 K27-altered or pontine location) or treatment for recurrent or progressive disease (except for oligodendroglioma, IDH- mutant and 1p19q codeleted or astrocytoma IDH-mutant);
  vii. One of the following for ovarian cancer, fallopian tube cancer, or peritoneal cancers (a-e):
  a) Carcinosarcoma (malignant mixed Mullerian tumors) of the ovary;
  b) Clear cell carcinoma of the ovary;
  c) Grade 1 endometrioid carcinoma;
  d) Mucinous carcinoma of ovary; e) Low-grade serous carcinoma;

  5. For ovarian cancer, fallopian tube cancer, or peritoneal cancer: Request is for recurrent therapy (e.g., previous treatment with regimen containing carboplatin, cisplatin, or oxaliplatin);
  6. Prescribed in combination with Mekinist;
  7. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  8. For pediatric members, documentation of member’s current body weight (in kg);
  9. Request meets one of the following (a or b): a. Dose does not exceed one of the following (i or ii): i. Adults: both of the following (a and b):
     a) 300 mg per day; b) 4 capsules per day;
     ii. Pediatric members: FDA approved maximum recommended dose (see Section V); b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN
     Approval duration:
     Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
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  CLINICAL POLICY Dabrafenib E. Pediatric Low-Grade Glioma (must meet all):

  1. Diagnosis of LGG (WHO grade 1 or 2);
  2. Prescribed by or in consultation with an oncologist;
  3. Age is between 1 to < 18 years;
  4. Disease is positive for a BRAF V600E mutation;
  5. Prescribed in combination with Mekinist;
  6. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  7. Documentation of member’s current body weight (in kg);
  8. Requests meets one of the following (a or b): a. Dose does not exceed the FDA approved maximum recommended dose (see Section V);
     b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
     Prescribed regimen must be FDA-approved or recommended by NCCN
     Approval duration:
     Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
     F. Histiocytic Neoplasms (off-label) (must meet all):
  9. Diagnosis of one of the following histiocytic neoplasms (a or b): a. Erdheim-Chester disease; b. Langerhans Cell histiocytosis;
  10. Prescribed by or in consultation with a hematologist or oncologist;
  11. Age ≥ 18 years;
  12. Disease is positive for a BRAF V600E mutation;
  13. Tafinlar is prescribed as a single agent;
  14. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  15. Request meets one of the following (a or b): a. Dose does not exceed both of the following (I and ii):
      i. 300 mg per day; ii. 4 capsules per day;
      b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less G. Other diagnoses/indications (must meet 1 or 2):
  16. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 5 of 12

  CLINICAL POLICY Dabrafenib CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

  2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
     II. Continued Therapy A. All Indications in Section I (must meet all):
  3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tafinlar for a covered indication and has received this medication for at least 30 days;
  4. Member is responding positively to therapy;
  5. For Tafinlar requests, member must use generic dabrafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
  6. For pediatric members, documentation of member’s current body weight (in kg);
  7. If request is for a dose increase, request meets one of the following (a or b):
     a. New dose does not exceed one of the following (i, ii, or iii): i. BRAF V600E mutation-positive solid tumor: one of the following (1 or 2):
     1) Adults: both of the following (a and b):
     a) 300 mg per day; b) 4 capsules per day;
     2) Pediatric members: FDA approved maximum (see Section V); ii. Pediatric LGG: FDA approved maximum (see Section V);
     iii. All other indications: both of the following (1 and 2):
     1) 300 mg per day; 2) 4 capsules per day; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
     Approval duration:
     Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
     B. Other diagnoses/indications (must meet 1 or 2):
  8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 6 of 12

  CLINICAL POLICY Dabrafenib CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

  2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
     III. Diagnoses/Indications for which coverage is NOT authorized:
     A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents.
     IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ATC: anaplastic thyroid cancer BRAF: B-Raf proto-oncogene, serine/ threonine kinase FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
     Not applicable Appendix C: Contraindications/Boxed Warnings None reported IDH: isocitrate dehydrogenase LGG: low grade glioma NSCLC: non-small cell lung cancer WHO: World Health Organization Appendix D: General Information
     • Nearly half of patients with melanoma have a BRAF mutation gene. The most common forms of the BRAF mutation are V600E (80-90%) and V600K (10-20%).
     • Tafinlar can potentiate the activity of the mitogen-activated protein kinases (MAPK) pathway in cells with wild-type BRAF and could accelerate the growth of some tumors with wild-type BRAF. • Examples of solid tumors that may be BRAF V600E mutation-positive include, but are not limited to, the following: biliary tract cancer, high grade glioma (glioblastoma, anaplastic pleomorphic xanthoastrocytoma, anaplastic astrocytoma, astroblastoma, anaplastic ganglioglioma, and anaplastic oligodendroglioma), low grade glioma (astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, pilocytic astrocytoma, choroid plexus papilloma, gangliocytoma/ganglioglioma), adenocarcinoma of small intestine, pancreas, or anus, mixed ductal/adenoneuroendocrine carcinoma, neuroendocrine carcinoma of colon, ameloblastoma of mandible, combined small cell- Page 7 of 12

  CLINICAL POLICY Dabrafenib squamous carcinoma of lung, mucinous-papillary serous adenocarcinoma of peritoneum, gastrointestinal stromal tumor.
  V. Dosage and Administration
  Indication Dosing Regimen Melanoma, NSCLC, ATC 150 mg (two 75 mg capsules) PO BID Maximum Dose 300 mg/day 300 mg/day BRAF V600E mutation- positive solid tumors The recommended duration of treatment in the adjuvant melanoma setting is until disease recurrence or unacceptable toxicity for up to 1 year. The recommended duration of treatment for all other indications is until disease progression or unacceptable toxicity. Adults: 150 mg (two 75 mg capsules) PO BID Pediatric patients: Capsules: • 26-37 kg: 75 mg (one 75 mg capsule) PO BID • 38-50 kg: 100 mg (two 50 mg capsules) PO BID • ≥ 51 kg: 150 mg (two 75 mg capsules) PO BID Tablets for oral suspension: • 8 to 9 kg: 20 mg (two 10 mg tablets) PO BID • 10 to 13 kg: 30 mg (three 10 mg tablets) PO BID • 14 to 17 kg: 40 mg (four 10 mg tablets) PO BID
  • 18 to 21 kg: 50 mg (five 10 mg tablets) PO BID • 22 to 25 kg: 60 mg (six 10 mg tablets) PO BID
  • 26 to 29 kg: 70 mg (seven 10 mg tablets) PO BID
  • 30 to 33 kg: 80 mg (eight 10 mg tablets) PO BID
  • 34 to 37 kg: 90 mg (nine 10 mg tablets) PO BID
  • 38 to 41 kg: 100 mg (ten 10 mg tablets) PO BID
  • 42 to 45 kg: 110 mg (eleven 10 mg tablets) PO BID
  • 46 to 50 kg: 130 mg (thirteen 10 mg tablets) PO BID
  • ≥ 51 kg: 150 mg (fifteen 10 mg tablets) PO BID
  Pediatric LGG The recommended duration of treatment is until disease progression or unacceptable toxicity.
  Capsules:
  • 26-37 kg: 75 mg (one 75 mg capsule) PO BID • 38-50 kg: 100 mg (two 50 mg capsules) PO BID • ≥ 51 kg: 150 mg (two 75 mg capsules) PO BID See dosing regimen Tablets for oral suspension: • 8 to 9 kg: 20 mg (two 10 mg tablets) PO BID • 10 to 13 kg: 30 mg (three 10 mg tablets) PO BID • 14 to 17 kg: 40 mg (four 10 mg tablets) PO BID
  • 18 to 21 kg: 50 mg (five 10 mg tablets) PO BID Page 8 of 12

  CLINICAL POLICY Dabrafenib Indication Dosing Regimen Maximum Dose • 22 to 25 kg: 60 mg (six 10 mg tablets) PO BID
  • 26 to 29 kg: 70 mg (seven 10 mg tablets) PO BID
  • 30 to 33 kg: 80 mg (eight 10 mg tablets) PO BID
  • 34 to 37 kg: 90 mg (nine 10 mg tablets) PO BID
  • 38 to 41 kg: 100 mg (ten 10 mg tablets) PO BID
  • 42 to 45 kg: 110 mg (eleven 10 mg tablets) PO BID
  • 46 to 50 kg: 130 mg (thirteen 10 mg tablets) PO BID
  • ≥ 51 kg: 150 mg (fifteen 10 mg tablets) PO BID
  The recommended duration of treatment is until disease progression or unacceptable toxicity. VI. Product Availability
  • Capsules: 50 mg, 75 mg • Tablet for oral suspension: 10 mg VII.