Subject: Stivarga SGM 1809-A P2025a

Drug

STIVARGA  (regorafenib)

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 Indications¹

Colorectal Cancer

Stivarga is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if RAS wild-type, an anti-epidermal growth factor receptor (EGFR) therapy.

Gastrointestinal Stromal Tumors

Stivarga is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Hepatocellular Carcinoma

Stivarga is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

Compendial Uses²

• Advanced or metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma
• Appendiceal neoplasms and cancers
• Ewing sarcoma
• Osteosarcoma
• Soft tissue sarcoma
  • Angiosarcoma
  • Epithelioid hemangioendothelioma
  • Non-adipocytic sarcoma (including extremity/body wall, head/neck and retroperitoneal/intra-abdominal soft tissue sarcomas)
  • Phyllodes tumor of the breast
  • Rhabdomyosarcoma
• Uterine sarcoma

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

Coverage Criteria

Colorectal Cancer (CRC)^1-4

Authorization of 12 months may be granted for treatment of advanced or metastatic colorectal cancer, including appendiceal adenocarcinoma and anal adenocarcinoma, as a single agent, when the member has progressed on previous treatment with all the following regimens unless the member has a contraindication or intolerance:

• Fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy (with or without bevacizumab).
• If RAS mutation status is negative (wild-type), an anti-epidermal growth factor receptor (EGFR) therapy, such as Erbitux (cetuximab) or Vectibix (panitumumab), for rectal cancer, appendiceal adenocarcinoma, anal adenocarcinoma, or left-sided colon cancer.

Gastrointestinal Stromal Tumor (GIST)^1,2

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

• The requested medication will be used as a single agent for locally advanced, residual, unresectable, tumor rupture, or recurrent/metastatic GIST following disease progression on imatinib and either sunitinib or ripretinib.
• The requested medication will be used for treatment of residual, unresectable, tumor rupture, or recurrent/metastatic GIST in combination with everolimus for disease progression after the member has failed at least four FDA-approved therapies (e.g., imatinib, sunitinib, ripretinib, avapritinib).
• The requested medication will be used as a single agent for treatment of succinate dehydrogenase (SDH)-deficient GIST.

Hepatocellular Carcinoma^1,2

Authorization of 12 months may be granted for subsequent treatment of hepatocellular carcinoma, as a single agent.

Soft Tissue Sarcomas²

Authorization of 12 months may be granted for treatment of angiosarcoma, epithelioid hemangioendothelioma, rhabdomyosarcoma, borderline/malignant Phyllodes tumor of the breast, and non-adipocytic sarcoma (including extremity/body wall, head/neck and retroperitoneal/intra-abdominal soft tissue sarcomas), as a single agent.

Osteosarcoma²

Authorization of 12 months may be granted for subsequent treatment of relapsed/refractory or metastatic osteosarcoma as a single agent.

Ewing Sarcoma²

Authorization of 12 months may be granted for subsequent treatment of relapsed (with or without radiation), progressive, or metastatic Ewing sarcoma as a single agent.

Uterine Sarcoma²

Authorization of 12 months may be granted for subsequent treatment of advanced, recurrent/metastatic, or inoperable uterine sarcoma as a single agent.

Appendiceal Neoplasms and Cancers²

Authorization of 12 months may be granted for subsequent treatment of recurrent, progressive, or extraperitoneal appendiceal neoplasms and cancers, as a single agent, when the member has progressed on previous treatment with the following regimens unless the member has a contraindication or intolerance:

• Fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy (with or without bevacizumab).

Continuation of Therapy

Gastrointestinal Stromal Tumor (GIST)

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for treatment of GIST when there is no evidence of unacceptable toxicity while on the current regimen.

All Other Indications

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for all other indications 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. Stivarga [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; February 2025.
2. The NCCN Drugs & Biologics Compendium® © 2026 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed February 3, 2026.
3. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. Version 4.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf.https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed July 14, 2025.
4. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 4.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.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.

March 25, 2026