Cigna Stivarga (regorafenib) Coverage Update

Coverage Criteria for Stivarga (regorafenib)

inv-01: FDA-Approved Indications — Colon/Rectal/Appendiceal

Covered for FDA‑approved indications when ALL of the following are met

Colon, Rectal, or Appendiceal Cancer (FDA) approval: Approve for 1 year if ALL: (A) Patient is >= 18 years of age; AND (B) patient has advanced or metastatic disease; AND (C) patient has been previously treated with a fluoropyrimidine (examples include capecitabine and 5‑fluorouracil); AND (D) patient has been previously treated with oxaliplatin; AND (E) patient has been previously treated with irinotecan.

inv-02: FDA-Approved Indications — GIST

Gastrointestinal Stromal Tumor (FDA)

GIST approval: Approve for 1 year if BOTH: (A) Patient is >= 18 years of age; AND (B) patient meets ONE of the following: (i) Patient has tried BOTH imatinib AND met ONE of: (1) tried sunitinib; OR (2) is intolerant to sunitinib and has tried Qinlock (ripretinib tablets); OR (ii) medication is used for succinate dehydrogenase (SDH)-deficient disease (per guideline allowance for earlier use).

inv-03: FDA-Approved Indications — HCC

Hepatocellular Carcinoma (FDA)

Hepatocellular carcinoma approval: Approve for 1 year if BOTH: (A) Patient is >= 18 years of age; AND (B) patient has been previously treated with one systemic regimen (examples include atezolizumab plus bevacizumab, bevacizumab, sorafenib, lenvatinib, nivolumab, tremelimumab‑actl, or durvalumab).

inv-04: Other Uses — Biliary Tract Cancers

Other Uses with Supportive Evidence — Biliary Tract Cancers

Biliary tract cancers: Approve for 1 year if BOTH: (A) Patient is >= 18 years of age; AND (B) patient has tried at least one systemic therapy (examples include cisplatin/gemcitabine, FOLFOX, capecitabine, or oxaliplatin).

inv-05: Other Uses — Sarcomas and Bone Cancer

Other Uses with Supportive Evidence — Bone Cancer, Soft Tissue Sarcoma, Uterine Sarcoma

Bone Cancer: Approve for 1 year if ALL: (A) Patient is >= 18 years of age; AND (B) patient has relapsed/refractory or metastatic disease; AND (C) patient has tried one systemic chemotherapy regimen (examples include cisplatin, doxorubicin, methotrexate, ifosfamide, cyclophosphamide, etoposide, topotecan, irinotecan, vincristine, temozolomide); AND (D) diagnosis is ONE of: Ewing sarcoma, mesenchymal chondrosarcoma, or osteosarcoma.

Soft Tissue Sarcoma: Approve for 1 year if ALL: (A) Patient is >= 18 years of age; AND (B) patient has advanced or metastatic disease; AND (C) patient has ONE of: borderline/malignant phyllodes tumor of the breast, epithelioid hemangioendothelioma, non-adipocytic sarcoma, pleomorphic rhabdomyosarcoma, or angiosarcoma.

Uterine Sarcoma: Approve for 1 year if ALL: (A) Patient is >= 18 years of age; AND (B) patient has recurrent, advanced, inoperable, or metastatic disease; AND (C) patient has tried at least one systemic regimen (examples include doxorubicin, docetaxel, gemcitabine, ifosfamide, dacarbazine, epirubicin, or vinorelbine).

Stivarga (regorafenib tablets) is not medically necessary for ANY other use(s) beyond the indications and uses specifically listed in this policy.

Any indication or use that is not explicitly listed under the policy’s covered FDA‑approved indications or the defined Other Uses with Supportive Evidence is considered not medically necessary and is not covered.

Covered Regimens and Regimen Context

Indication	Regimen (per NCCN)	Line of therapy / NCCN category	Coverage stance
Appendiceal neoplasms and cancers	Stivarga (regorafenib) as a single agent or other listed regimens (examples include Fruzaqla® [fruquintinib] or Lonsurf® [trifluridine and tipiracil] with or without bevacizumab)	Second-line or subsequent therapy; recommended as subsequent therapy after progression through available regimens	Covered with criteria
Biliary tract cancers	Stivarga as a subsequent therapy listed under 'Other Recommended' regimens	Subsequent therapy (category 2B)	Covered with criteria
Bone cancer (osteosarcoma, Ewing sarcoma, mesenchymal chondrosarcoma)	Stivarga as single-agent 'Preferred Regimen' for osteosarcoma and as 'Other Recommended Regimen' for Ewing sarcoma and mesenchymal chondrosarcoma	Second-line therapy for relapsed/refractory or metastatic disease (osteosarcoma category 1; Ewing category 2A; mesenchymal chondrosarcoma category 2B)	Covered with criteria
Colon cancer / Rectal cancer	Stivarga as single agent for advanced or metastatic disease not previously treated with Stivarga (after progression through available regimens except Stivarga, Fruzaqla®, or Lonsurf® with/without bevacizumab)	Subsequent therapy (recommended as subsequent single-agent therapy)	Covered with criteria
Gastrointestinal stromal tumor (GIST)	Stivarga as single agent; combination with everolimus is 'Useful in Certain Circumstances'; SDH-deficient disease may have earlier use per NCCN	Preferred third-line agent after imatinib and sunitinib (category 1); if intolerant to sunitinib, ripretinib (Qinlock®) is an alternative; SDH-deficient disease recommendations include first-line options in certain circumstances	Covered with criteria
Hepatocellular carcinoma	Stivarga as subsequent treatment (examples of prior systemic regimens listed in NCCN)	Subsequent therapy (category 1)	Covered with criteria
Soft tissue sarcoma (selected histologies) and uterine sarcoma	Stivarga as single-agent subsequent therapy for listed histologies (nonadipocytic sarcoma, pleomorphic rhabdomyosarcoma, borderline/malignant phyllodes, epithelioid hemangioendothelioma, angiosarcoma) and as an 'Other Recommended Regimen' for uterine sarcoma	Second-line or subsequent therapy (generally category 2A for these histologies)	Covered with criteria

Coding and Age Requirements

Covered codesmixed

No codes listed

inv-09: Age — patient must be ≥ 18 years

Minimum agePatient must be ≥ 18 years of age for all covered indications listed.

ApplicabilityApplies to FDA‑approved indications (Colon/Rectal/Appendiceal, GIST, Hepatocellular carcinoma) and listed other uses with supportive evidence (e.g., biliary tract, bone cancer, soft tissue sarcoma, uterine sarcoma).

Source noteAge threshold is specified in each indication's approval criteria (see individual indication requirements).

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior Authorization is recommended for prescription benefit coverage of Stivarga. All approvals are provided for the duration noted in the criteria (typically 1 year when criteria are met).

Prior authorization recommended for Stivarga (regorafenib).
Approvals typically granted for 1 year when coverage criteria are met.

Step Therapy

Prior Therapy Requirements

Many FDA‑approved and supportive‑evidence indications require prior systemic therapies or specific prior agents before approval will be granted. Examples include prior exposure to fluoropyrimidine, oxaliplatin, and irinotecan for colorectal cancers; imatinib (and often sunitinib or ripretinib) for GIST; at least one prior systemic regimen for hepatocellular carcinoma; and at least one prior systemic chemotherapy regimen for certain bone cancers. For biliary tract cancers, at least one prior systemic therapy is required. Review the indication‑specific criteria for required prior therapies.

Line of Therapy Specifications

inv-17: second-line | third-line — top-level node specifying line of therapy requirements and sequencing

Line of therapy notes

Line of therapy notes: Stivarga is positioned as subsequent (second-line or later) therapy for most indications; for GIST it is a preferred third-line agent per NCCN; SDH‑deficient GIST may be considered earlier (including first‑line in certain SDH‑deficient cases) as described in guidelines.

Biomarker and Molecular Requirements

inv-18: SDH (succinate dehydrogenase) deficiency — biomarker definition/requirement

Biomarker nameSuccinate dehydrogenase (SDH) deficiency

Role in policySDH deficiency is a defined biomarker used to identify SDH‑deficient GIST and allows Stivarga to be used under the SDH‑deficient disease pathway (including first‑line consideration per revisions).

inv-16: SDH-deficient disease — definition and context for SDH-deficient GIST

DefinitionSDH‑deficient disease refers to gastrointestinal stromal tumors (GIST) with succinate dehydrogenase deficiency.

Policy implicationFor GIST, Stivarga may be used when the medication is intended for SDH‑deficient disease; recent revisions added allowance for first‑line use in SDH‑deficient GIST.

Guideline support

Definitions and Drug Identity

inv-15: Stivarga (regorafenib) — drug identity key/value

Generic nameRegorafenib (oral tablets)

Brand nameStivarga

Primary indications (policy)Indicated/covered for metastatic colorectal cancer after prior chemotherapy, GIST after prior imatinib and sunitinib (or for SDH‑deficient disease), and hepatocellular carcinoma after sorafenib; approvals granted for 1 year when criteria are met.

Drug classOral multikinase/tyrosine kinase inhibitor

Background

Regorafenib (Stivarga) is an oral multikinase inhibitor used in oncology. This policy defines coverage for specific FDA‑approved indications and selected off‑label uses with supportive evidence; uses outside those listed are considered not medically necessary and are excluded from coverage.

OpenPayer

Stivarga (regorafenib) coverage