Print

Date Printed: June 26, 2017: 11:39 AM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-14

Original Effective Date: 09/15/14

Revised: 08/15/16

Subject: Ramucirumab (Cyramza™) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Ramucirumab (Cyramza), a fully human monoclonal antibody that binds with high affinity to the extracellular domain of vascular endothelial growth factor receptor 2 (VEGFR2), preventing the binding of VEGF-A, VEGF-C, and VEGF-D, was approved by the U.S. Food and Drug Administration (FDA) in April 2014 for the treatment of advanced gastric cancer or gastro-esophageal junction adenocarcinoma, as a single-agent after prior fluoropyrimidine- or platinum-containing chemotherapy. In December 2014, the FDA expanded the approved use of ramucirumab to treat patients with metastatic non-small cell lung cancer (NSCLC).

The safety and efficacy of ramucirumab were evaluated in subjects (n=355) with locally advanced or metastatic gastric cancer (including adenocarcinoma of the gastro-esophageal junction [GEJ]) who previously received platinum- or fluoropyrimidine-containing chemotherapy in multicenter, double-blind, randomized clinical trial. Patients were required to have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Patients received either an intravenous infusion of ramucirumab 8 mg/kg (n=238) or placebo solution (n=117) every 2 weeks. The primary endpoint was overall survival; progression-free survival an additional outcome measure.

Efficacy results are summarized in table 1:

Table 1

Overall Response Rate and Duration of Response

 

Ramucirumab

N=238

Placebo

N=117

Overall Survival

Number of deaths (%)

179 (75%)

99 (85%)

     Median – months (95% CI)

5.2 (4.4, 5.7)

3.8 (2.8, 4.7)

     Hazard Ratio (95% CI)

0.78 (0.60, 0.998)

     Stratified Log-rank p-value

0.047

Progression-free Survival

Number of events (%)

199 (84%)

108 (92%)

     Median – months (95% CI)

2.1 (1.5, 2.7)

1.3 (1.3, 1.4)

     Hazard Ratio (95% CI)

0.48 (0.38, 0.62)

     Stratified Log-rank p-value

<0.001

Ramucirumab carries a boxed warning of hemorrhage. The most frequently reported adverse event was hypertension.

National Comprehensive Cancer Network (NCCN) Guidelines for Gastric Cancer (Version 1.2016) and Esophageal and Esophagogastric Junction Cancers (Version 1.2016) recommend ramucirumab as second-line treatment in those with advanced or metastatic disease. Additionally, NCCN guidelines for Lung Cancer (Version 4.2016) recommend ramucirumab in combination with docetaxel in patients with advanced or metastatic NSCLC who have experienced disease progression either during or after first-line therapy (category 2B recommendation). NCCN Guidelines for Colon Cancer (Verion 2.2016) and Rectal Cancer (Version 2.2016) recommend ramucirumab for advanced or metastatic disease after treatment failure.

POSITION STATEMENT:

Initiation of ramucirumab (Cyramza) meets the definition of medical necessity for members diagnosed with ANY of the following conditions when ALL associated criteria are met:

1. Colon cancer

a. Member’s disease is advanced or metastatic

b. Member’s disease is unresectable

c. Member has failed treatment with one of the following:

i. FOLFOX (fluorouracil, leucovorin, and oxaliplatin) with or without bevacizumab

ii. CapeOX (capecitabine and oxaliplatin) with or without bevacizumab

iii. 5-FU/leucovorin

iv. Capecitabine with or without bevacizumab

d. Use will be in combination with either of the following:

i. Irinotecan

ii. FOLFIRI (fluorouracil, leucovorin, and irinotecan)

e. The dose does not exceed 8 mg/kg every 2 weeks

2. Gastric cancer

a. Member’s disease is advanced or metastatic

b. Member has failed treatment with fluoropyrimidine or platinum-containing chemotherapy

c. Member demonstrates one of the following:

i. Karnofsky performance score greater than or equal to 60%

ii. ECOG performance score less than or equal to 2

d. Ramucirumab will be used as monotherapy or in combination with paclitaxel

e. The dose does not exceed 8 mg/kg every 2 weeks

3. Esophageal or Esophagogastric junction (EGJ) adenocarcinoma

a. Member’s disease is advanced or metastatic

b. Member has failed treatment with fluoropyrimidine or platinum-containing chemotherapy

c. Member demonstrates one of the following:

i. Karnofsky performance score greater than or equal to 60%

ii. ECOG performance score less than or equal to 2

d. Ramucirumab will be used as monotherapy or in combination with paclitaxel

e. The dose does not exceed 8 mg/kg every 2 weeks

4. Non-small cell lung cancer

a. Member’s disease is advanced or metastatic

b. Member has disease progression either during or after platinum-based chemotherapy with the following exceptions:

i. If EGFR positive disease, member has disease progression on an FDA-approved therapy for EGFR positive disease (e.g., afatinib, erlotinib)

ii. If ALK positive disease, member has disease progression on an FDA-approved therapy for ALK positive disease (e.g., crizotinib, ceritinib)

c. Member demonstrates an ECOG performance score less than or equal to 2

d. Ramucirumab will be used in combination with docetaxel

e. The dose does not exceed 10 mg/kg every 3 weeks

5. Rectal cancer

a. Member’s disease is advanced or metastatic

b. Member’s disease is unresectable

c. Member has failed treatment with one of the following:

i. FOLFOX (fluorouracil, leucovorin, and oxaliplatin) with or without bevacizumab

ii. CapeOX (capecitabine and oxaliplatin) with or without bevacizumab

iii. 5-FU/leucovorin

iv. Capecitabine with or without bevacizumab

d. Use will be in combination with either of the following:

i. Irinotecan

ii. FOLFIRI (fluorouracil, leucovorin, and irinotecan)

e. The dose does not exceed 8 mg/kg every 2 weeks

Duration of approval: 6 months

Continuation of ramucirumab (Cyramza) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue or another health plan in the past 2 years, OR the member previously met all indication-specific initiation criteria

2. Member’s disease has not progressed during treatment with ramucirumab

3. The dose does not exceed diagnosis specific limitation:

a. Colon cancer: 8 mg/kg every 2 weeks

b. Gastric cancer: 8 mg/kg every 2 weeks

c. Gastro-esophageal junction adenocarcinoma: 8 mg/kg every 2 weeks

d. Non-small cell lung cancer: 10 mg/kg every 3 weeks

e. Rectal cancer: 8 mg/kg every 2 weeks

Duration of approval: 6 months

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• Gastric cancer, Gastro-esophageal junction adenocarcinoma: 8 mg/kg IV every 2 weeks

• Non-small cell lung cancer: 10 mg/kg IV every 3 weeks

• Premedicate with IV histamine H1-antagonist (e.g., diphenhydramine) prior to each infusion

Dose Adjustments

Infusion Related Reactions (IRR)

Hypertension

Proteinuria

Wound Healing Complications

Arterial Thromboembolic Events, Gastrointestinal Perforation, or Grade 3 or 4 Bleeding

Drug Availability

100 mg/10 mL solution, single-dose vial; 500 mg/50 mL solution, single-dose vial

PRECAUTIONS:

Boxed Warning

Contraindications

None

Precautions/Warnings

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J9308

Injection, ramucirumab, 5 mg

ICD-10 Diagnoses Codes That Support Medical Necessity (Effective 10/01/15)

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

C16.5 

Malignant neoplasm of lesser curvature of stomach, unspecified

C16.6 

Malignant neoplasm of greater curvature of stomach, unspecified

C16.8 

Malignant neoplasm of overlapping sites of stomach

C16.9 

Malignant neoplasm of stomach, unspecified

C17.0

Malignant neoplasm of duodenum

C17.1

Malignant neoplasm of jejunum

C17.2

Malignant neoplasm of ileum

C17.8

Malignant neoplasm of other specified sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified site

C18.0

Malignant neoplasm of cecum

C18.1

Malignant neoplasm of appendix

C18.2

Malignant neoplasm of ascending colon

C18.3

Malignant neoplasm of hepatic flexure

C18.4

Malignant neoplasm of transverse colon

C18.5

Malignant neoplasm of splenic flexure

C18.6

Malignant neoplasm of descending colon

C18.7

Malignant neoplasm of sigmoid colon

C18.8

Malignant neoplasm of overlapping sites of colon

C18.9

Malignant neoplasm of colon, unspecified

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.8

Malignant neoplasm of other sites of rectum, rectosigmoid junction, and anus

C33

Malignant neoplasm of trachea

C34.00 – C34.92

Malignant neoplasm of bronchus or lung

C78.00 – 78.02

Secondary malignant neoplasm of lung

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

D37.1 

Neoplasm of uncertain behavior of stomach

D37.2 

Neoplasm of uncertain behavior of small intestine

D37.4 

Neoplasm of uncertain behavior of colon

D37.5 

Neoplasm of uncertain behavior of rectum

D37.8 

Neoplasm of uncertain behavior of other specified digestive organs

D37.9 

Neoplasm of uncertain behavior of digestive organ, unspecified

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

Table 2: Eastern Cooperative Oncology Group (ECOG) Performance Status

Grade

Description

0

Fully active, able to carry on all pre-disease performance without restriction

1

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

2

Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours

3

Capable of only limited self-care, confined to bed or chair more than 50% of waking hours

4

Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

5

Dead

RELATED GUIDELINES:

None

OTHER:

Table 3: Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

Grade

Description

1

Mild; asymptomatic or mild symptoms; clinical diagnostic observations only; intervention not indicated

2

Moderate; minimal, local or noninvasive intervention indicated; limited age-appropriate instrumental activities of daily living

3

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living

4

Life-threatening consequences; urgent intervention indicated

5

Death related to adverse event

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015 Jul 16]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2015 June16]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2016 June 16]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited2016 June 16]. Available from: http://www.thomsonhc.com/.
  5. Eli Lily. Cyramza (ramucirumab) injection. 2014 [cited 2016 June 16]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c6080942-dee6-423e-b688-1272c2ae90d4/.
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Colon Cancer, v. 2.2016 [cited 2016 June 16]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  7. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Esophageal and Esophagogastric Junction Cancers, v. 1.2016 [cited 2016 June 16]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  8. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Gastric Cancer, v. 1.2016 [cited 2016 June 16]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  9. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Non-small cell lung cancer, v. 4.2016 [cited 2016 June 16]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  10. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Rectal Cancer, v. 2.2016 [cited 2016 June 16]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  11. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2014 [cited 2016 June 16]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  12. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2014 [cited 2016 June 16]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 07/13/16.

GUIDELINE UPDATE INFORMATION:

09/15/14

New Medical Coverage Guideline.

02/15/15

Revision to guideline; consisting of description, position statement, dosage, administration, coding

08/15/15

Review and revision to guideline; consisting of position statement, coding, references.

11/01/15

Revision: ICD-9 Codes deleted.

01/01/16

Annual HCPCS coding update: added code J9308 and deleted codes C9025 and J9999.

07/15/16

Revision to guideline; consisting of updating position statement and ICD10 codes

08/15/16

Review and revision to guideline; consisting of updating position statement and references.

Date Printed: June 26, 2017: 11:39 AM