ModifiedHealth NetPolicy CP PHAR.107

Clinical Policy: Regorafenib (Stivarga)

Defines medical necessity criteria, authorization requirements, and approval durations for regorafenib (Stivarga) for FDA-approved and selected off-label oncology indications for Health Net lines of business.

Policy Summary

PayerHealth Net

PolicyClinical Policy: Regorafenib (Stivarga)

Policy CodePolicy CP PHAR.107

Change Type2Q 2025 annual review — added indications and revised HCC criteria

Effective DateDec 1, 2012

Next Review Date

Key ActionObtain prior authorization with supporting clinical documentation demonstrating criteria are met (including documentation of prior therapies and current response for continuation).

SourceLink

POLICY UPDATE CHANGES

For HCC, removed requirement for Child-Pugh class A disease per NCCN.

Added off-label criteria set for uterine sarcoma per NCCN.

Commercial approval duration modified to 12 months or duration of request, whichever is less; continuation approvals consolidated to 12 months.

Additional coverable cancers (gliosarcoma, H3-mutated high-grade glioma) were added.

For hepatocellular carcinoma (HCC), the requirement for Child-Pugh class A disease was removed.

An off-label criteria set for uterine sarcoma per NCCN was added.

References were reviewed and updated as part of the 2Q 2025 annual review.

12 monthsTypical commercial approval

6 monthsMedicaid/HIM approval

160 mgMax dose (days 1-21)

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

40 mg tabProduct availability

2Q 2025Annual review

3New indications added

Coverage Criteria for Regorafenib (Stivarga)

Other diagnoses/indications

H. Other diagnoses/indications (must meet 1 or 2):

ANY of the following

For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid): follow the applicable no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid.
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 the applicable policy for recent label changes per line of business.
For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid): follow the applicable 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.
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 none of the above 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.

Common Initial Therapy Requirements

Continuation / Renewal Criteria

Prior Authorization

Prior Authorization Required

Prior authorization is required for continuation of Stivarga (regorafenib). Prior authorization requirements have been updated per policy revisions; providers must submit required clinical documentation at the time of request. Coverage decisions remain subject to terms, member benefits, and eligibility. Non-covered indications: requests for uses that are not FDA‑approved or not supported by NCCN or peer‑reviewed literature (when applicable) may be denied.

Prior authorization required for continuation therapy
Prior authorization requirements updated — confirm current policy version and payer edits
Required clinical documentation must be provided (see criteria group below)
Coverage decisions remain subject to member benefit limitations and eligibility
Non‑covered indications risk if request lacks FDA approval or guideline/literature support

Documentation Required

Step Therapy and Prior-Line Requirements

Coverage requirement	Details / Policy language
Generic-first requirement for brand requests
For brand Stivarga requests, member must use generic regorafenib if available unless contraindicated or clinically significant adverse effects are experienced.
Indications requiring prior lines of therapy before regorafenib may be authorized
Metastatic colorectal cancer: prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti‑VEGF therapy, and if RAS wild‑type an anti‑EGFR therapy (or systemic chemotherapy per Appendix B for pMMR/MSS).
Gastrointestinal stromal tumor (GIST): disease previously treated with imatinib and sunitinib (or ripretinib/Qinlock if intolerant to sunitinib) unless contraindicated or clinically significant adverse effects.
Hepatocellular carcinoma (HCC): prescribed as second‑ or subsequent‑line therapy; previously treated with sorafenib (per Appendix B/NCCN guidance).
Continuation / renewal requirement
For continuation requests, member must be currently receiving Stivarga via the benefit or have documentation of ≥30 days of therapy; member must be responding positively to therapy; brand requests must trial generic regorafenib if available unless contraindicated.

Indication	Therapeutic alternatives / required prior lines
Metastatic colorectal cancer (CRC)
Examples of systemic chemotherapy and targeted agents per Appendix B: fluorouracil (5‑FU), irinotecan (Camptosar), oxaliplatin (Eloxatin), bevacizumab (Avastin), ramucirumab (Cyramza), trifluridine/tipiracil (Lonsurf), cetuximab (Erbitux), panitumumab (Vectibix), and checkpoint inhibitors where indicated (e.g., pembrolizumab) — prior exposure to fluoropyrimidine-, oxaliplatin-, and irinotecan‑based regimens, an anti‑VEGF, and if RAS wild‑type an anti‑EGFR is required before regorafenib per policy.
Gastrointestinal stromal tumor (GIST)
Prior treatment with imatinib (Gleevec) and sunitinib (Sutent); ripretinib (Qinlock) may be used if intolerant to sunitinib. Regorafenib may be used after progression on these agents; off‑label combination with everolimus noted after progression on approved therapies.
Hepatocellular carcinoma (HCC)
Regorafenib reserved as second‑ or subsequent‑line therapy after prior sorafenib per Appendix B/NCCN guidance; dosing and prior‑therapy requirements specified in criteria set.
Other systemic regimens referenced
Appendix B lists chemotherapy regimens that may be considered prior therapies in CRC and other settings (FOLFOX, CAPEOX, FOLFIRI, FOLFOXIRI, IROX) and relevant biologics/checkpoint inhibitors; these are examples of therapeutic alternatives that may be required prior to regorafenib depending on indication.

Provider Requirements and Authorization Process

Prior Authorization

Prior authorization required with supporting clinical documentation

Prior authorization is required for regorafenib (Stivarga) and must be supported by clinical documentation demonstrating that the applicable coverage criteria are met; refer to formulary, non‑formulary, and off‑label policies when applicable.

Follow line-of-business policies for formulary/non‑formulary routing as referenced in the policy (e.g., CP.CPA.190, HIM.PA.33, CP.PMN.255).

Prior Authorization

Prior authorization for continuation: show benefit, dosing and generic‑first compliance

Prior authorization is required for continuation requests; the request must document a positive response to therapy and comply with dosing limits and formulary/generic‑first requirements.

New doses must not exceed 160 mg PO daily on days 1–21 of each 28‑day cycle unless supported by practice guidelines or peer‑reviewed literature with prescriber evidence.
For brand requests, trial/use of generic regorafenib is required if available unless contraindicated or clinically significant adverse effects are documented.

Coding and Dose Limits

Maximum daily dose — 160 mg/day

Maximum daily dose160 mg/day (maximum recommended dose on days 1-21 of each 28-day cycle)

Dosing schedule160 mg PO once daily for the first 21 days of each 28-day cycle

Applicable indicationsSpecifies this maximum for CRC, GIST, and HCC dosing regimens

Quantity Limits and Product Availability

regorafenib (Stivarga) — product quantity/dose information (160)

Product strengthTablet: 40 mg

Quantity limit / dose unitRegorafenib (Stivarga) quantity limit documented as 160 (mg/day)

Standard dosing regimen160 mg PO once daily (days 1-21 of a 28-day cycle)

Definitions and Key Terms

Stivarga / regorafenib — definition: oral multikinase/VEGFR inhibitor

Drug class / mechanismOral multikinase inhibitor with activity against VEGF/VEGFR and other kinases

Common brand/generic namesStivarga (regorafenib)

Typical formulationOral tablet (40 mg)

Child-Pugh — Child-Pugh score and classes

Scoring overviewChild-Pugh score is determined by total points from five parameters: bilirubin, albumin, INR, ascites, and encephalopathy

Class A5-6 points

Class B

Background

Regorafenib (Stivarga) is an oral multikinase inhibitor with activity against vascular endothelial growth factor receptors (VEGFR) and other kinases. It is available as a 40 mg tablet and is indicated for certain previously treated metastatic cancers; dosing commonly used is 160 mg/day given orally for the first 21 days of each 28-day cycle. The drugs mechanism as a multi-kinase/VEGFR inhibitor underlies its use across colorectal cancer, GIST, hepatocellular carcinoma, and selected off-label oncology indications when criteria are met.

Revision History

2025-02-05policy_revision

2Q 2025 annual review removed the Child-Pugh class A requirement for hepatocellular carcinoma (HCC) per updated NCCN guidance.

2025-02-05policy_addition

2Q 2025 annual review added an off-label criteria set for uterine sarcoma per NCCN.

2025-02-05policy_additionLatest

Policy Summary

PayerHealth Net

PolicyClinical Policy: Regorafenib (Stivarga)

Policy CodePolicy CP PHAR.107

Change Type2Q 2025 annual review — added indications and revised HCC criteria

Effective DateDec 1, 2012

Next Review Date

Key ActionObtain prior authorization with supporting clinical documentation demonstrating criteria are met (including documentation of prior therapies and current response for continuation).

SourceLink

On This Page

Documentation required: medical records demonstrating current use of Stivarga or at least 30 days of therapy, evidence of clinical benefit/response, dosing history, rationale for any dose increase, and documentation of trial of generic regorafenib first (unless contraindicated or intolerance). Prescriber must supply supporting literature when requesting non‑FDA‑approved dosing.

Medical records showing current receipt of Stivarga via benefit or ≥30 days of therapy
Clinical documentation of positive response to therapy
Dosing history and dates of administration
If increasing dose, documentation that new dose does not exceed 160 mg daily on days 1–21 of a 28‑day cycle or peer‑reviewed evidence supporting higher/off‑label dosing
Evidence of trial of generic regorafenib or documentation of contraindication/intolerance

Continuation / Renewal Criteria

Covered when ALL of the following are met:

ALL of the following

Member is currently receiving medication via the Centene benefit, or documentation supports that the member is currently receiving Stivarga for a covered indication and has received this medication for at least 30 days.
Member is responding positively to therapy (clinical improvement or disease control documented).
- ANY of the following
  - New dose does not exceed 160 mg per day on days 1 to 21 of each 28‑day cycle.
  - New dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).
For brand Stivarga requests, the member must use generic regorafenib first, if available, unless contraindicated or clinically significant adverse effects are experienced (prescriber must document contraindication/intolerance).
Prescribed regimen must be FDA‑approved or recommended by NCCN; for off‑label regimens, prescriber must provide supporting peer‑reviewed evidence.

Documentation Required

Continuation Therapy — Documentation

Continuation therapy documentation: approval for continuation requires demonstration of ongoing benefit and adherence to dosing limits and generic‑first rules. For continuation, documentation must show member is currently receiving Stivarga via the benefit or has received it for at least 30 days.

Show ongoing clinical benefit or disease stabilization
Adherence to dosing limits (≤160 mg daily on days 1–21 of each 28‑day cycle unless supported by evidence)
Evidence of generic regorafenib trial or documented contraindication/intolerance
Duration of prior therapy (≥30 days) must be documented

Prior Authorization

Prior authorization criteria updated per 2Q 2025 policy revisions

Policy revisions (2Q 2025) add indications and revise HCC criteria; prior authorization criteria and applicable coverage determinations should be applied consistent with these updates and state Medicaid provisions when they conflict.

For HCC the Child‑Pugh class A requirement was removed per NCCN (2Q 2025 update).
When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid provisions take precedence.

Step Therapy

Generic‑first requirement for brand Stivarga requests

For brand Stivarga requests, the member must use generic regorafenib if it is available unless there is a documented contraindication or clinically significant adverse effects.

This generic‑first requirement applies to initial and continuation requests per the policy language.

Step Therapy

Refer non‑listed or non‑formulary uses to no‑coverage/non‑formulary/off‑label policies

If the requested use is not listed in this policy or the drug is non‑formulary, refer the request to the applicable no‑coverage, non‑formulary, or off‑label use policy for required prior treatment trials and routing.

Refer to CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary no‑coverage routing; CP.CPA.190, HIM.PA.103, CP.PMN.16 for non‑formulary routing; and CP.CPA.09, HIM.PA.154, CP.PMN.53 for off‑label use.

Documentation Required

Submit office notes, labs, and other clinical documentation with PA requests

Providers must submit supporting clinical documentation (for example, office chart notes, laboratory results, or other clinical information) to demonstrate the member meets the policy approval criteria.

Include relevant prior therapy history, response assessments, and rationale for off‑label dosing when applicable.

Denial Risk

Denial risk if required documentation is not provided

Failure to submit required documentation (office notes, lab results, or other clinical information) supporting that the member has met all approval criteria may result in denial of the request.

Ensure documentation of prior therapies, current response, and any contraindications to generic therapy are provided.

Denial Risk

Non‑FDA indications require off‑label documentation per policy

Requests for indications that are not FDA‑approved and not addressed in this policy are not authorized unless sufficient documentation of efficacy and safety is provided per the applicable off‑label use policy.

Off‑label requests must meet the off‑label policy documentation standards (e.g., CP.CPA.09, HIM.PA.154, CP.PMN.53).

Note

Coverage subject to benefit terms, exclusions, and state Medicaid precedence

Coverage decisions are subject to the terms, conditions, exclusions, and limitations of the member’s benefit documents; policy determinations may be denied if contract terms are not met.

When state Medicaid provisions conflict with this policy, state Medicaid rules take precedence.

Note

Contract terms reminder and prohibited unauthorized use

Providers and members are bound by the contractual terms and conditions expressed in their agreements; unauthorized copying, use, or distribution of this clinical policy is prohibited.

By providing services or submitting claims, providers and members agree to be bound by these terms.

progressive (per NCCN) — Progressive disease qualifier per NCCN

Definition sourcePer NCCN disease qualifier referenced in policy update

Meaning in policy context'Progressive' refers to disease progression as defined by NCCN guidance used to qualify certain indications

RelevanceUsed to determine eligibility for off-label and updated CNS/HCC indications per 2Q 2025 policy revisions

2Q 2025 annual review added additional coverable central nervous system cancer indications including gliosarcoma and H3‑mutated high‑grade glioma.