CurrentViva Health PlanPolicy IC-0199

Cyramza® (ramucirumab) Intravenous Coverage

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This policy governs prior authorization, medical necessity, dosing, renewal, and billing requirements for intravenous Cyramza in adult members with specified advanced or metastatic cancers. Coverage is limited to defined tumor types, treatment lines, combinations, biomarkers, prior therapies, and response or toxicity requirements.

Policy Summary

PayerViva Health Plan

PolicyCyramza® (ramucirumab) Intravenous Coverage

Policy CodePolicy IC-0199

Change TypeNo material change

Effective DateN/A

Last ReviewSep 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation supporting the cancer diagnosis, disease status, treatment line, prior therapies, regimen, required biomarker or AFP result, and renewal response or toxicity assessment.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsPrior authorization validity

6Cancer indications addressed

180 BU/14 daysMaximum dose for CRC, gastric/esophageal/GEJ cancers, and HCC

240 BU/14 daysMaximum dose for NSCLC

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CurrentViva Health PlanPolicy IC-0199

Cyramza® (ramucirumab) Intravenous Coverage

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Policy Summary

PayerViva Health Plan

PolicyCyramza® (ramucirumab) Intravenous Coverage

Policy CodePolicy IC-0199

Change TypeNo material change

Effective DateN/A

Last ReviewSep 1, 2026

Next Review DateN/A

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsPrior authorization validity

6Cancer indications addressed

180 BU/14 daysMaximum dose for CRC, gastric/esophageal/GEJ cancers, and HCC

240 BU/14 daysMaximum dose for NSCLC

38Covered diagnosis codes

Medical Necessity and Authorization Criteria

Universal Initial Criteria

Initial coverage requires all universal criteria plus one applicable indication-specific criteria set.

Universal requirements

All of the following
- Member is at least 18 years of age.
- Member does not have uncontrolled severe hypertension.
- Member has not had a surgical procedure within the preceding 2 weeks and does not have a surgical wound that has not fully healed.

Colorectal Cancer

Covered when all applicable colorectal cancer requirements are met.

All of the following

Cyramza is used in combination with irinotecan or FOLFIRI (irinotecan, folinic acid/leucovorin, and fluorouracil).
One treatment setting
- Initial treatment
  - Disease is unresectable and metastatic.
  - Cyramza is used after previous FOLFOX or CapeOX within the past 12 months.Within the past 12 months
- Subsequent therapy
  - Disease has progressed and is advanced or metastatic.

Gastric, Esophageal, and Esophagogastric Junction Cancers

Covered when all applicable gastric, esophageal, or esophagogastric junction cancer requirements are met.

All of the following

Member has adenocarcinoma histology.
Cyramza is used as subsequent therapy.
Cyramza is used as a single agent, in combination with paclitaxel, or in combination with an irinotecan-based regimen.
Disease setting
- Member has advanced, recurrent, or metastatic disease.
- Member is not a surgical candidate.

Hepatocellular Carcinoma

Covered when all applicable hepatocellular carcinoma requirements are met.

All of the following

Cyramza is used as a single agent.
Cyramza is used as subsequent therapy for progressive disease.
Member has an alpha-fetoprotein (AFP) level of at least 400 ng/mL.AFP ≥ 400 ng/mL

Non-Small Cell Lung Cancer

Covered when the disease setting is met and either the docetaxel or erlotinib pathway is met.

All of the following

Disease setting
- One disease setting
  - Member has recurrent, advanced, or metastatic disease, excluding locoregional recurrence or symptomatic local disease without evidence of disseminated disease.
  - Member has mediastinal lymph node recurrence with prior radiation therapy.
One regimen pathway
- Docetaxel pathway
  - Cyramza is used in combination with docetaxel.

Pleural Mesothelioma

Covered when both the regimen and treatment-line requirement are met.

All of the following

Cyramza is used in combination with gemcitabine.
Cyramza is used as subsequent therapy.

Thymic Carcinoma

Covered when Cyramza is combined with carboplatin and paclitaxel and one treatment-setting pathway is met.

All of the following

Cyramza is used in combination with carboplatin and paclitaxel.
One treatment setting
- Cyramza is used as preoperative therapy for surgically resectable disease when an R0 resection is considered uncertain.
- Cyramza is used as postoperative therapy after an R1 or R2 resection.
- Cyramza is used as first-line therapy for recurrent, advanced, or metastatic disease.

Renewal Criteria

Renewal requires all applicable continuation criteria.

All of the following

Member continues to meet the universal and relevant indication-specific criteria, including applicable concomitant therapy requirements and performance status.
Disease response is demonstrated by stabilization of disease or a decrease in the size of the tumor or tumor spread, unless otherwise specified.
There is no unacceptable toxicity from the drug, including hemorrhage, arterial thromboembolic events, uncontrolled hypertension, infusion-related reactions, severe proteinuria, nephrotic syndrome, gastrointestinal perforation, impaired wound healing, posterior reversible encephalopathy syndrome, thyroid dysfunction, or worsening of pre-existing hepatic impairment.

For NSCLC, recurrent, advanced, or metastatic disease coverage excludes locoregional recurrence or symptomatic local disease without evidence of disseminated disease. Coverage may also apply to mediastinal lymph node recurrence when the member has received prior radiation therapy.

Billing Codes and Dose Limits

Covered HCPCS CodesHCPCSCovered

J9308

Injection, ramucirumab, 5 mg; 1 billable unit = 5 mg

Covered NDCsNDCCovered

00002-7669-xx	Cyramza 100 mg/10 mL solution, single-dose vial
00002-7678-xx	Cyramza 500 mg/50 mL solution, single-dose vial

Covered Diagnosis CodesICD-10Covered

C15.3	Malignant neoplasm of upper third of esophagus
C15.4	Malignant neoplasm of middle third of esophagus
C15.5	Malignant neoplasm of lower third of esophagus
C15.8	Malignant neoplasm of overlapping sites of esophagus
C15.9	Malignant neoplasm of esophagus, unspecified
C16.0	Malignant neoplasm of cardia
C16.1	Malignant neoplasm of fundus of stomach
C16.2	Malignant neoplasm of body of stomach
C16.3	Malignant neoplasm of pyloric antrum
C16.4	Malignant neoplasm of pylorus

1–10 of 26

1/3

Covered Diagnosis CodesICD-10Covered

C22.0	Liver cell carcinoma
C22.8	Malignant neoplasm of liver, primary, unspecified as to type
C22.9	Malignant neoplasm of liver, not specified as primary or secondary
C33	Malignant neoplasm of trachea
C34.00	Malignant neoplasm of main bronchus
C34.01	Malignant neoplasm of right main bronchus
C34.02	Malignant neoplasm of left main bronchus
C34.10	Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11	Malignant neoplasm of upper lobe, right bronchus or lung
C34.12	Malignant neoplasm of upper lobe, left bronchus or lung

1–10 of 41

1/5

HCC Alpha-Fetoprotein Threshold

IndicationHepatocellular carcinoma (HCC)

BiomarkerAlpha-fetoprotein (AFP)

Minimum AFP level≥ 400 ng/mL

Maximum Dose: Gastric/Esophageal/GEJ Cancers, CRC, and HCC

IndicationsGastric, esophageal, esophagogastric junction/gastroesophageal junction cancers, colorectal cancer, and hepatocellular carcinoma

Maximum dose180 billable units

Authorization, Documentation, and Denial Risks

Prior Authorization

Six-Month Prior Authorization

Obtain prior authorization before treatment. Initial authorization is valid for 6 months (180 days), and renewal may be requested every 6 months thereafter (180 days).

Submit the request before the initial treatment period or current authorization expires.
Renewal requests must document continued eligibility and response criteria.

Documentation Required

Universal Eligibility and Safety Requirements

Confirm that the member meets all universal eligibility and safety requirements before requesting authorization.

Member is at least 18 years of age.
Member does not have uncontrolled severe hypertension.

Policy and Therapy Background

Cyramza (ramucirumab) is an intravenous antiangiogenic therapy that inhibits tumor blood-vessel formation. Coverage is limited to selected adults with advanced, recurrent, metastatic, or otherwise specified cancers, including colorectal, gastric, esophageal, gastroesophageal junction, hepatocellular, non-small cell lung, pleural mesothelioma, and thymic carcinomas. Coverage depends on the applicable treatment line, regimen, prior therapy, biomarker or alpha-fetoprotein status, and evidence of continued clinical benefit without unacceptable toxicity.

Clinical Definitions

R0 Resection

TermR0 resection

Residual tumorNo residual tumor after resection

Policy contextPreoperative therapy may apply when R0 resection is considered uncertain

R1 Resection

TermR1 resection

Residual tumorMicroscopic residual tumor after resection

Policy contextPostoperative therapy may apply after R1 resection

Treatment-Line Requirements

First-line

Covered first-line treatment requires one of the following colorectal cancer pathways.

One CRC first-line pathway

Cyramza is used as initial treatment for unresectable metastatic disease after previous FOLFOX or CapeOX within the past 12 months.Within the past 12 months
Cyramza is used as subsequent therapy for progression of advanced or metastatic disease; the member has not previously received irinotecan-based therapy; and the member has previously received oxaliplatin-based therapy.

Second-line

Covered second-line treatment requires subsequent therapy in a qualifying indication-specific setting.

Subsequent therapy

Required Biomarker and Laboratory Findings

EGFR Test Requirement

BiomarkerEGFR exon 19 deletion or L858R mutation

Required resultPositive disease

Testing requirementDetected by an FDA-approved or Clinical Laboratory Improvement Amendments (CLIA)-compliant test

T790M Requirement

BiomarkerT790M

Required resultNegative

Applicable treatmentNSCLC treatment with erlotinib

Indication-Specific Treatment Regimens

Coverage status	Indication	Covered regimen and requirements
Covered	Colorectal cancer	Ramucirumab with irinotecan or FOLFIRI. For initial treatment, disease must be unresectable and metastatic after FOLFOX or CapeOX within the past 12 months. For subsequent therapy, disease must have progressed and the member must have prior oxaliplatin-based therapy without prior irinotecan-based therapy.

Coverage status	Indication	Covered regimen and requirements
Covered	Gastric, esophageal, or esophagogastric/gastroesophageal junction adenocarcinoma	Ramucirumab alone, with paclitaxel, or with an irinotecan-based regimen. The member must have adenocarcinoma histology, receive subsequent therapy, and have advanced, recurrent, or metastatic disease or not be a surgical candidate.

Coverage status	Indication	Covered regimen and requirements
Covered	Hepatocellular carcinoma	Ramucirumab monotherapy as subsequent therapy for progressive disease when the alpha-fetoprotein level is at least 400 ng/mL.

Coverage status	Indication	Covered regimen and requirements
Covered	Non-small cell lung cancer	Ramucirumab with docetaxel as subsequent therapy for first progression after initial systemic therapy, with no prior docetaxel or ramucirumab; or with erlotinib for EGFR exon 19 deletion or L858R mutation-positive disease confirmed by an FDA-approved or CLIA-compliant test. Erlotinib use may be first-line or continued after progression on erlotinib plus ramucirumab, and requires T790M-negative disease.

Coverage status	Indication	Covered regimen and requirements
Covered	Pleural mesothelioma	Ramucirumab with gemcitabine as subsequent therapy. Coverage may also apply to pericardial mesothelioma and tunica vaginalis testis mesothelioma.

Coverage status	Indication	Covered regimen and requirements
Covered	Thymic carcinoma	Ramucirumab with carboplatin and paclitaxel. Treatment may be preoperative when R0 resection is uncertain, postoperative after R1 or R2 resection, or first-line for recurrent, advanced, or metastatic disease. Ramucirumab may continue as maintenance monotherapy.

Policy Summary

PayerViva Health Plan

PolicyCyramza® (ramucirumab) Intravenous Coverage

Policy CodePolicy IC-0199

Change TypeNo material change

Effective DateN/A

Last ReviewSep 1, 2026

Next Review DateN/A

SourceLink

On This Page

Member has not previously received irinotecan-based therapy.

Member has previously received oxaliplatin-based therapy.

Cyramza is used as subsequent therapy for first progression after initial systemic therapy.

Member has not previously received docetaxel or ramucirumab.

Erlotinib pathway

Cyramza is used in combination with erlotinib.
Disease has an EGFR exon 19 deletion or L858R mutation detected by an FDA-approved or CLIA-compliant test.
Treatment setting
- Cyramza is used as first-line therapy.
- Cyramza is continued after disease progression on combination erlotinib and ramucirumab therapy for asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited progression.
Disease is T790M negative.T790M negative

Maximum intervalPer 14 days

Maximum Dose: NSCLC

IndicationNon-small cell lung cancer (NSCLC)

Maximum dose240 billable units

Maximum intervalPer 14 days

Maximum Dose: Pleural Mesothelioma and Thymic Carcinoma

IndicationsPleural mesothelioma and thymic carcinoma

Maximum dose240 billable units

Maximum intervalPer 21 days

Member has not undergone surgery within the preceding 2 weeks and has no surgical wound that is not fully healed.

Unsupported block type: info

Unsupported block type: step_therapy

Unsupported block type: documentation

Unsupported block type: denial_risk

Denial Risk

Indication-Specific Criteria Not Met

Authorization should be denied when the requested use does not satisfy the applicable indication-specific coverage criteria.

The cancer type, histology, disease setting, treatment line, or surgical status does not match the policy.
The requested regimen or required concomitant therapy is not documented.
Required prior therapy or treatment sequencing is absent or inconsistent with the indication.
Required biomarker results, including EGFR and T790M status for applicable NSCLC therapy, are missing or do not qualify.
For HCC, AFP is below 400 ng/mL or the required progressive-disease and subsequent-therapy criteria are not met.

Denial Risk

Renewal Response or Safety Failure

Renewal requires continued satisfaction of universal and indication-specific criteria, evidence of treatment response, and no unacceptable toxicity. Renewal may be denied when response is inadequate, criteria are no longer met, or toxicity makes continued treatment unsafe.

Document stabilization of disease or a decrease in tumor size or tumor spread unless otherwise specified.
Confirm continued eligibility, required concomitant therapy, and other relevant criteria.
Assess for unacceptable toxicity, including hemorrhage, arterial thromboembolic events, uncontrolled hypertension, infusion reactions, severe proteinuria (>3 g/24 h), nephrotic syndrome, gastrointestinal perforation, impaired wound healing, PRES, thyroid dysfunction, or worsening hepatic impairment.

Billing Rule

Dose or Frequency Exceeds Policy Limits

Claims may be denied when billed units, dosing intervals, or administration patterns exceed the policy’s dosage and maximum-unit limits.

For gastric, esophageal, esophagogastric junction, gastroesophageal junction cancers, CRC, and HCC: maximum 180 billable units per 14 days; standard dose is 8 mg/kg IV every 14 days.
For NSCLC: maximum 240 billable units per 14 days; with docetaxel, standard dose is 10 mg/kg IV every 21 days.
For pleural mesothelioma and thymic carcinoma: maximum 240 billable units per 21 days; standard dose is 10 mg/kg IV every 21 days.
Do not bill excessive units, shortened intervals, or noncovered administration patterns.

Billing Rule

Medicare Coverage Policy Requirements

For Medicare members, follow applicable CMS coverage and claims-payment requirements in addition to the plan’s policy criteria.

Apply the Medicare Benefit Policy Manual, Pub. 100-2, Chapter 15, §50, for outpatient Part B drugs.
Check applicable National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs).
Use the CMS Medicare Coverage Database to identify applicable policies and payment guidance.

R2 Resection

TermR2 resection

Residual tumorMacroscopic residual tumor after resection

Policy contextPostoperative therapy may apply after R2 resection

dMMR/MSI-H

TermdMMR/MSI-H

MeaningDeficient mismatch repair or microsatellite instability-high status

CRC treatment considerationIf present, treatment should include checkpoint inhibitor immunotherapy when the member is a candidate

EGFR Mutation-Positive Disease

TermEGFR mutation-positive disease

Required mutationEGFR exon 19 deletion or L858R mutation

Disease contextA qualifying biomarker for NSCLC treatment with erlotinib

Cyramza is used as subsequent therapy for a qualifying colorectal cancer, gastric/esophageal/esophagogastric junction cancer, hepatocellular carcinoma, non-small cell lung cancer, or pleural mesothelioma setting described in the policy.

First-line

Covered first-line thymic carcinoma treatment requires one of the following treatment settings.

One thymic carcinoma treatment setting

Cyramza is used as preoperative therapy for surgically resectable disease when an R0 resection is considered uncertain.
Cyramza is used as postoperative therapy after an R1 or R2 resection.
Cyramza is used as first-line therapy for recurrent, advanced, or metastatic disease.

AFP Requirement

BiomarkerAlpha-fetoprotein (AFP)

Required resultAFP level of at least 400 ng/mL

Applicable indicationHepatocellular carcinoma subsequent therapy

CRC Biomarker Requirements

Qualifying biomarker statusDeficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) or POLE/POLD1 mutation with an ultra-hypermutated phenotype

Example thresholdTumor mutational burden greater than 50 mutations/Mb

CRC treatment considerationTreatment should include checkpoint inhibitor immunotherapy if the member is a candidate