Subject: Xeloda SGM 1993-A P2025

Drug

XELODA  (capecitabine)

Policy:

Indications

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications^1,2

Colorectal Cancer

• Xeloda is indicated for the adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen.
• Xeloda is indicated for the perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy.
• Xeloda is indicated for the treatment of patients with unresectable or metastatic colorectal cancer as a single agent of as a component of a combination chemotherapy regimen.

Breast Cancer

• Xeloda is indicated for the treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated.
• Xeloda is indicated for the 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

• Xeloda is indicated for the treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen.
• Xeloda is indicated for the 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

• Xeloda is indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.

Compendial Uses^3-8

• Ampullary adenocarcinoma
• Anal carcinoma
• Biliary tract cancers (including extrahepatic and intra-hepatic cholangiocarcinoma and gallbladder cancer)
• Breast cancer
• Cervical cancer
• Colorectal cancer (including anal adenocarcinoma and appendiceal adenocarcinoma)
• Esophageal and esophagogastric junction cancers
• Gastric cancer
• Gestational trophoblastic neoplasia
• Head and neck cancers (including very advanced head and neck cancer)
• Neuroendocrine and adrenal tumors
• Occult primary tumors (cancer of unknown primary)
• Ovarian cancer, fallopian tube cancer, and primary peritoneal cancer: epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, carcinosarcoma (malignant mixed Mullerian tumors), clear cell carcinoma, grade 1 endometrioid carcinoma, low-grade serious carcinoma/ovarian borderline epithelial tumor, mucinous cancer
• Pancreatic adenocarcinoma
• Penile cancer
• Small bowel adenocarcinoma
• Squamous cell skin cancer
• Thymomas and thymic carcinomas
• Vaginal cancer
• Vulvar cancer

All other indications are considered experimental/investigational and not medically necessary.

Coverage Criteria

Ampullary Adenocarcinoma³

Authorization of 12 months may be granted for treatment of ampullary adenocarcinoma.

Anal Carcinoma^3,6

Authorization of 12 months may be granted for treatment of squamous cell anal carcinoma when any of the following criteria are met:

• The requested medication will be used as concurrent chemoradiation in combination with mitomycin.
• The requested medication will be used with radiation after primary treatment of metastatic disease, as a single agent.

Biliary Tract Cancers^3,6,7

Authorization of 12 months may be granted for treatment of biliary tract cancers (including extrahepatic and intrahepatic cholangiocarcinoma and gallbladder cancer).

Breast Cancer^1-7

Authorization of 12 months may be granted for treatment of breast cancer when any of the following criteria are met:

• Member has human epidermal growth factor receptor 2 (HER2) negative advanced, recurrent unresectable, or metastatic disease or member had no response to preoperative systemic therapy, as a single agent or in combination with docetaxel.
• Member has early-stage HER2 negative postoperative residual disease, as a single agent.
• Member has HER2 positive advanced, recurrent unresectable, or metastatic disease or member had no response to preoperative systemic therapy, and the requested medication will be used as subsequent therapy in combination with trastuzumab and tucatinib or in combination with a HER2 inhibitor (e.g., margetuximab-cmkb [Margenza], trastuzumab [Herceptin], lapatinib [Tykerb], neratinib [Nerlynx]).
• The requested medication will be used in combination with ixabepilone for treatment of metastatic or locally advanced disease.
• Member has triple negative disease and meets one of the following criteria:
• The requested medication will be used as adjuvant therapy.
• The requested medication will be used as maintenance therapy following adjuvant chemotherapy.
• The requested medication will be used for advanced, recurrent unresectable, or metastatic disease or member had no response to preoperative systemic therapy, as a single agent or in combination with docetaxel.
• Member has brain metastases in breast cancer and the requested medication will be used as initial therapy or for recurrent or relapsed disease.

Cervical Cancer, Vaginal Cancer, and Vulvar Cancer³

Authorization of 12 months may be granted for cervical, vaginal, and vulvar cancer when all of the following criteria are met:

• The requested medication will be used as concurrent chemoradiation in combination with mitomycin.
• The requested medication will be used if cisplatin and carboplatin are unavailable.

Colorectal Cancer (CRC)^1-3,8

Authorization of 12 months may be granted for treatment of colorectal cancer, including anal adenocarcinoma and appendiceal adenocarcinoma.

Esophageal and Esophagogastric Junction Cancers^3,4,6

Authorization of 12 months may be granted for treatment of esophageal and esophagogastric junction cancers.

Gastric Cancer^,3,4,6,7

Authorization of 12 months may be granted for treatment of gastric cancer.

Gestational Trophoblastic Neoplasia³

Authorization of 12 months may be granted for treatment of gestational trophoblastic neoplasia, as a single agent.

Head and Neck Cancers^3,6,7

Authorization of 12 months may be granted for treatment of head and neck cancers (including very advanced head and neck cancer), as a single agent.

Neuroendocrine and Adrenal Tumors³

Authorization of 12 months may be granted for treatment of any of the following:

• Member has neuroendocrine and adrenal tumors of the gastrointestinal tract, lung, or thymus (carcinoid tumors).
• Member has neuroendocrine and adrenal tumors of the pancreas, in combination with temozolomide or as a component of CAPEOX (capecitabine and oxaliplatin) regimen.
• Member has extrapulmonary poorly differentiated disease/large or small cell disease/mixed neuroendocrine-non-neuroendocrine neoplasm, in combination with temozolomide or with concurrent or sequential radiation.
• Member has well differentiated grade 3 neuroendocrine and adrenal tumors, in combination with temozolomide or as a component of CAPEOX (capecitabine and oxaliplatin) regimen.

Occult Primary Tumors (cancer of unknown primary)^3,6

Authorization of 12 months may be granted for treatment of occult primary tumors, as a single agent or as a component of CAPEOX (capecitabine and oxaliplatin) regimen.

Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer^3,6

Authorization of 12 months may be granted for treatment of any of the following:

• As single agent therapy for persistent or recurrent epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, carcinosarcoma (malignant mixed Mullerian tumors), clear cell carcinoma, or grade 1 endometrioid carcinoma.
• Member has low-grade serous carcinoma/borderline epithelial tumor and the requested medication will be used as single agent therapy for platinum-sensitive or platinum-resistant recurrence.
• Member has mucinous carcinoma of the ovary and one of the following criteria is met:
• The requested medication will be used in combination with oxaliplatin as neoadjuvant or adjuvant treatment.
• The requested medication will be used as a single agent or in combination with oxaliplatin for treatment of persistent or relapsed/recurrent disease.

Pancreatic Adenocarcinoma^3,6

Authorization of 12 months may be granted for treatment of pancreatic adenocarcinoma.

Penile Cancer³

Authorization of 12 months may be granted for treatment of penile cancer, as a single agent.

Small Bowel Adenocarcinoma³

Authorization of 12 months may be granted for treatment of small bowel adenocarcinoma.

Squamous Cell Skin Cancer³

Authorization of 12 months may be granted as a single agent for treatment of squamous cell skin cancer when one of the following criteria is met:

• Disease is locally advanced, unresectable, distant metastatic, recurrent, or regional disease that is inoperable or incompletely resected and member is ineligible for or has progressed on immune checkpoint inhibitors and clinical trials.
• The requested medication will be used as treatment for severe refractory field cancerization/confluent epidermal dysplasia that has progressed on oral retinoids.

Thymomas and Thymic Carcinomas³

Authorization of 12 months may be granted for treatment of thymomas and thymic carcinomas in combination with gemcitabine.

Continuation of Therapy

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for an indication listed in the coverage criteria section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Place of Service:

Outpatient

The above policy is based on the following references:

1. Xeloda [package insert]. South San Francisco, CA: Genentech, Inc.; December 2022.
2. Capecitabine [package insert]. Lehi, UT: CivicaScript, LLC; February 2025.
3. The NCCN Drugs & Biologics Compendium® © 2025 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed July 16, 2025.
4. Clinical Pharmacology powered by ClinicalKey. Philadelphia PA. Elsevier. c2025. http://www.clinicalkey.com. Accessed July 16, 2025.
5. Ixempra [package insert]. Princeton, NJ: R-Pharm US LLC; February 2022.
6. Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; 2025. http://online.lexi.com. Accessed July 16, 2025.
7. Micromedex® (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com. Accessed July 16, 2025.
8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. Version 4.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. Accessed July 14, 2025.

Copyright Aetna Inc. All rights reserved. Pharmacy 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.

January 20, 2026