XELODA, Capecitabine Form

Capecitabine (Xeloda®) is nucleoside metabolic inhibitor with antineoplastic activity. FDA Approved Indication(s) Xeloda is indicated for the treatment of: • Colorectal Cancer o Adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen.
o Perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. o Treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen. • Breast Cancer o Treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline-or taxane-containing chemotherapy is not indicated.
o Treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. • Gastric, Esophageal, or Gastroesophageal Junction Cancer o Treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen.
o Treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. • Pancreatic Cancer o Adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. 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.
It is the policy of health plans affiliated with Centene Corporation® that Xeloda is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Colorectal Cancer (must meet all):
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CLINICAL POLICY Capecitabine

1. Diagnosis of colorectal cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced;
2. Request meets one of the following (a, b, c, or d): a. Monotherapy (unresectable or metastatic disease, or adjuvant treatment): Dose does not exceed 1,250 mg/m2 twice a day on Days 1 to 14, every 21 days (if adjuvant treatment: maximum of 8 cycles); b. In combination with oxaliplatin-containing regimen (unresectable or metastatic disease, or adjuvant treatment): Dose does not exceed 1,000 mg/m2 twice a day on Days 1 to 14, every 21 days; c. For perioperative treatment, one of the following (i or ii):
   i. With concomitant radiation therapy: Dose does not exceed 825 mg/m2 twice a day; ii. Without radiation therapy: Dose does not exceed 1,250 mg/m2 twice a day; d. 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: 6 months
   B. Breast Cancer (must meet all):
3. Diagnosis of breast cancer and one of the following (a or b):
   a. Disease is recurrent, advanced, metastatic, or unresponsive to preoperative systemic therapy; b. Xeloda is prescribed as adjuvant or maintenance therapy;

4. Prescribed by or in consultation with an oncologist;

   3. Age ≥ 18 years;
   4. Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced;
   5. Request meets one of the following (a or b): a. Dose does not exceed 1,250 mg/m2 twice a day on Days 1 to 14, every 21 days; 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: 6 months C. Gastric, Esophageal or Gastroesophageal Junction Cancer (must meet all):
   6. Diagnosis of gastric, esophageal or gastroesophageal junction cancer;
   7. Prescribed by or in consultation with an oncologist;
   8. Age ≥ 18 years;
   9. Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced;
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   CLINICAL POLICY Capecitabine

5. Request meets one of the following (a. b, or c): a. Dose does not exceed 625 mg/m2 twice a day on Days 1 to 21, every 21 days (maximum of 8 cycles); b. Dose does not exceed 1,000 mg/m2 twice a day on Days 1 to 14, every 21 days; c. 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: 6 months
   D. Pancreatic Cancer (must meet all):
   
   1. Diagnosis of pancreatic cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced;
   5. Request meets one of the following (a or b): a. Dose does not exceed 830 mg/m2 twice a day on Days 1 to 21, every 28 days (maximum of 6 cycles); 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: 6 months
      E. NCCN Recommended Uses (off-label) (must meet all):
   6. Prescribed for one of the following diagnoses (a – m):
      a. Ampullary adenocarcinoma; b. Anal carcinoma;
      c. Gestational trophoblastic neoplasia d. Advanced head and neck cancer; e. Hepatobiliary cancer (i, ii, or iii): i. Extrahepatic cholangiocarcinoma; ii. Gallbladder cancer; iii. Intrahepatic cholangiocarcinoma; f. Neuroendocrine tumor of the pancreas, gastrointestinal tract, lung, or thymus; g. Extrapulmonary neuroendocrine carcinoma (i or ii):
      i. Large and small carcinoma; ii. Mixed neuroendocrine-non-neuroendocrine neoplasm; h. Occult primary cancer (cancer of unknown origin); i. Ovarian or fallopian tube or primary peritoneal cancer; j. Penile cancer; k. Small bowel adenocarcinoma; l. Squamous cell skin cancer; m. Thymoma or thymic carcinoma;

6. Prescribed by or in consultation with an oncologist;

   3. Age ≥ 18 years; Page 3 of 11

   CLINICAL POLICY Capecitabine

7. Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced;
8. Dose is within FDA maximum limit for any FDA approved indication or 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: 6 months F. Other diagnoses/indications (must meet 1 or 2):
9. 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: 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: 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: 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):
10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Xeloda for a covered indication and has received this medication for at least 30 days;
11. Member is responding positively to therapy;
    
    3. Member must use generic capecitabine, unless contraindicated or clinically significant adverse effects are experienced;

12. If request is for a dose increase, request meets one of the following (a - e): a. Colorectal cancer, one of the following (i, ii, or iii):
    i. Monotherapy (unresectable or metastatic disease, or adjuvant treatment): New dose does not exceed 2,500 mg/m2 total daily dose on Days 1 to 14, every 21 days (if adjuvant treatment: maximum of 8 cycles); ii. In combination with oxaliplatin-containing regimen (unresectable or metastatic disease, or adjuvant treatment): New dose does not exceed 2,000 mg/m2 total daily dose on Days 1 to 14, every 21 days; iii. For perioperative treatment, one of the following (1 or 2):
    1) With concomitant radiation therapy: New dose does not exceed 1,650 2) Without radiation therapy: New dose does not exceed 2,500 mg/m2 total mg/m2 total daily dose; daily dose; Page 4 of 11

    CLINICAL POLICY Capecitabine b. Breast cancer: New dose does not exceed 2,500 mg/m2 total daily dose on Days 1 to 14, every 21 days c. Gastric, esophageal, or gastroesophageal junction cancer, one of the following (i or ii): i. New dose does not exceed 1,250 mg/m2 total daily dose on Days 1 to 21, every 21 days (maximum of 8 cycles); ii. New dose does not exceed 2,000 mg/m2 total daily dose on Days 1 to 14, every 21 days; d. Pancreatic cancer: New dose does not exceed 1,660 mg/m2 total daily dose on Days 1 to 21, every 28 days (maximum of 6 cycles);
    e. 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: 12 months B. Other diagnoses/indications (must meet 1 or 2):

13. 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: 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: 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: 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 – 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 FDA: Food and Drug Administration
       NCCN: National Comprehensive Cancer Network Appendix B: Therapeutic Alternatives
       Not applicable
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    CLINICAL POLICY Capecitabine Appendix C: Contraindications/Boxed Warnings • Contraindication(s): severe hypersensitivity reactions to fluorouracil or capecitabine • Boxed warning(s): increased risk of bleeding with concomitant use of vitamin k antagonists V. Dosage and Administration
    Maximum Dose 2,500 mg/m2 total daily dose 2,500 mg/m2 total daily dose 2,000 mg/m2 total daily dose Indication Colorectal Cancer
    Breast Cancer Gastric, Esophageal, or Gastroesophageal Junction Cancer Dosing Regimen Adjuvant, unresectable or metastatic treatment • Single agent: 1,250 mg/m2 PO BID for the first 14 days of each 21-day cycle • Combination with oxaliplatin-containing regimen: 1,000 mg/m2 PO BID for the first 14 days for each 21-day cycle

    • For adjuvant treatment: maximum of 8 cycles; For unresectable or metastatic treatment: until disease progression or unacceptable toxicity Perioperative treatment • With concomitant radiation therapy: 825 mg/m2 PO BID
      • Without radiation therapy: 1,250 mg/m2 PO BID Advanced or metastatic treatment
      • Single agent or combination with docetaxel: 1,000 mg/m2 or 1,250 mg/m2 PO BID for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity Unresectable or metastatic treatment
      • In combination with platinum-containing chemotherapy: 625 mg/m2 PO BID on days 1 to 21 of each 21-day cycle (maximum of 8 cycles) OR
      In combination with oxaliplatin: 850 mg/m2 or 1,000 mg/m2 PO BID for first 14 days of each 21-day cycle until disease progression or unacceptable toxicity
      • HER2-overexpressing metastatic adenocarcinoma
      • In combination with cisplatin and trastuzumab: 1,000 mg/m2 PO BID for first 14 days of each 21-day cycle until disease progression or unacceptable toxicity
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    CLINICAL POLICY Capecitabine Indication Pancreatic Cancer Dosing Regimen • In combination with gemcitabine: 830 mg/m2 PO BID for the first 21 days of each 28-day cycle (maximum of 6 cycles)
    Maximum Dose 1,660 mg/m2 total daily dose VI. Product Availability
    Tablets: 150 mg, 500 mg VII.