CurrentmhnPolicy CP.PHAR.119

Ramucirumab (Cyramza)

Defines medical necessity criteria, dosing limits, authorized indications (FDA-approved and selected NCCN off-label uses), prior authorization/documentation requirements, approval durations by line of business, and HCPCS coding implications for ramucirumab (Cyramza).

Policy Summary

Payermhn

PolicyRamucirumab (Cyramza)

Policy CodePolicy CP.PHAR.119

Change TypeAnnual reviews with revised indications and durations

Effective DateJun 1, 2015

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results, other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

1Q 2026 annual review: for HCC, revised progression on sorafenib to subsequent therapy use per NCCN; removed appendiceal adenocarcinoma indication and added thymic carcinoma as off-label indication per NCCN; revised approval durations for Medicaid / HIM to 12 months and for Commercial to '6 months or duration of request, whichever is less'; references reviewed and updated.

RT4: clarified FDA-Approved Indications section to specify use in adults per updated FDA labeling.

1Q 2025 annual review: for colorectal cancer, added criteria for off-label use in appendiceal adenocarcinoma as second-line or subsequent therapy; for HCC, removed confirmation of Child-Pugh class A status per NCCN; revised Appendix B.

1Q 2024 annual review: per NCCN added off-label indication criteria for mesothelioma.

1Q 2023 annual review: for esophageal, EGJ and gastric cancers, removed 'advanced' requirement and added requirement for confirmation of Child-Pugh class A for HCC; removed 'progressive' cancer requirement for HCC.

1Q 2022 annual review: revised criteria allowing combination with irinotecan +/- fluorouracil for esophageal/EGJ/gastric cancers and added requirement for unresectable/locally advanced/recurrent/metastatic disease per NCCN.

5FDA-approved indications listed

Coverage Summary

Scope summary: This policy defines medical necessity criteria, dosing limits, authorized indications (both FDA‑approved and selected NCCN off‑label uses), prior authorization and documentation requirements, approval durations by line of business, and HCPCS coding implications for ramucirumab (Cyramza). Coverage stance: covered_with_criteria. Background overview: Ramucirumab (Cyramza) is a human VEGFR2 antagonist with multiple FDA‑approved oncology indications (including gastric/EGJ adenocarcinoma, NSCLC combinations, metastatic colorectal cancer with FOLFIRI, and hepatocellular carcinoma with AFP requirement) and additional NCCN‑recommended off‑label uses. Approval durations are specified by line of business: Medicaid / HIM – 12 months; Commercial – 6 months or duration of request, whichever is less. Coverage aligns with FDA labeling and NCCN recommendations.

Initial Therapy Criteria

Continuation Therapy Criteria

II. Continuation/Renewal Criteria

All indications in Section I must meet all of the following for continuation:

Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Cyramza for a covered indication and has received this medication for at least 30 days
Member is responding positively to therapy
If request is for a dose increase, one of:
- Esophageal/EGJ/gastric cancer, CRC, HCC: New dose does not exceed 8 mg/kg every 2 weeks8 mg/kg every 2 weeks
- NSCLC in combination with docetaxel: New dose does not exceed 10 mg/kg on day 1 of a 21-day cycle10 mg/kg day 1 of 21-day cycle
- NSCLC in combination with erlotinib: New dose does not exceed 10 mg/kg every 2 weeks10 mg/kg every 2 weeks
- 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

Unproven / Exclusions

Exceptions: Non‑FDA approved indications not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety per the applicable off‑label use policy (CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid). Prescribers requesting off‑label regimens must submit supporting evidence such as practice guidelines or peer‑reviewed literature.

Applicable Codes

Drug HCPCS CodeHCPCS

J9308

Injection, ramucirumab, 5 mg

Provider Actions

Documentation Required

Submit supporting clinical documentation

Provider must submit supporting clinical documentation including office notes, laboratory results, and other relevant clinical information to demonstrate the member meets all approval criteria.

Prior Authorization

Prior authorization may be required for companion agents

Prior authorization may be required for companion agents depending on line of business and regimen. Agents called out include paclitaxel, fluorouracil, irinotecan, docetaxel, erlotinib, and gemcitabine. For off‑label regimens, the prescriber must submit supporting evidence (practice guidelines or peer‑reviewed literature).

Clinical Evidence

REACH-2 randomized phase 3 (Zhu et al., Lancet Oncol 2019)Key HCC trial

Cyramza Prescribing Information; NCCN guidelines 2025-2026References

Evidence summary: The key trial supporting HCC use is the REACH‑2 randomized phase 3 trial (Zhu et al., Lancet Oncol 2019). This policy references the Cyramza Prescribing Information and multiple NCCN guidelines (various 2025–2026 versions) to inform indications, dosing limits, and biomarker requirements.

Background

Background details: Ramucirumab (Cyramza) is a human VEGFR2 antagonist. FDA‑approved oncology indications include treatment of advanced or metastatic gastric/EGJ adenocarcinoma (single agent or with paclitaxel), combinations in NSCLC (with erlotinib for EGFR exon 19/21 sensitizing mutations and with docetaxel after platinum therapy), combination with FOLFIRI for metastatic colorectal cancer, and single‑agent therapy for hepatocellular carcinoma in patients with AFP ≥ 400 ng/mL after sorafenib. Dosing limits and administration align with FDA labeling and NCCN recommendations (e.g., typical dose limits of 8 mg/kg every 2 weeks for many indications and 10 mg/kg dosing for specified NSCLC regimens). Required biomarkers include AFP ≥ 400 ng/mL for HCC and documented sensitizing EGFR mutations for erlotinib combinations.

Term	Definition
AFP	alpha fetoprotein
EGJ	esophagogastric junction
EGFR	epidermal growth factor receptor
FOLFIRI	fluorouracil, leucovorin, irinotecan
HCC	hepatocellular carcinoma
NCCN	National Comprehensive Cancer Network
NSCLC	non-small cell lung cancer
VEGFR2	vascular endothelial growth factor receptor 2

Revision History

09.15.21P&T 02.22 (1Q 2022 annual review)

10.24.22P&T 02.23 (1Q 2023 annual review)

1Q 2023 annual review: for esophageal, EGJ and gastric cancers, removed the 'advanced' requirement and added requirement for confirmation of Child‑Pugh class A for HCC; removed 'progressive' cancer requirement for HCC.

11.05.23P&T 02.24 (1Q 2024 annual review)

1Q 2024 annual review: per NCCN added off‑label indication criteria for mesothelioma.