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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-J0000-66

Original Effective Date: 11/15/06

Reviewed: 06/14/17

Revised: 07/15/17

Subject: Bevacizumab (Avastin®) 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

 

Previous Version

           

DESCRIPTION:

Bevacizumab (Avastin) is a humanized monoclonal antibody that inhibits the binding of vascular endothelial growth factor (VEGF) to its receptors, VEGFR-1 and VEGFR-2. This action neutralizes the biological activity of VEGF ultimately inhibiting the formation of new tumor vessels. Alone, bevacizumab is not directly cytotoxic; as such it is commonly used in combination with traditional cytotoxic treatment modalities including chemotherapy, radiation therapy, and hormonal therapy in the treatment of cancer.

Bevacizumab was initially approved by the US Food and Drug Administration (FDA) in February 2004 as a first-line treatment option for metastatic colorectal cancer in combination with 5-flourouracil (5-FU). The initial approval in colorectal cancer was expanded to include second-line therapy in June 2006. In October 2006, bevacizumab, in combination with carboplatin and paclitaxel, was FDA-approved for first-line treatment of locally advanced, recurrent, or metastatic non-squamous, non-small cell lung cancer (NSCLC). In February 2008, bevacizumab in combination with paclitaxel was approved for use in persons who had not previously received chemotherapy for metastatic HER2-negative breast cancer; however, in 2011, the FDA removed approval for the breast cancer indication after review of clinical data indicated that the drug did not prolong overall survival in breast cancer patients or provide sufficient benefit in slowing disease progression to outweigh the significant risk. In May 2009, the FDA granted bevacizumab accelerated approval for the treatment of glioblastoma in persons with disease that has progressed on prior therapy. In July 2009, bevacizumab was approved for treatment of metastatic renal cell carcinoma in combination with interferon-alfa. Bevacizumab has also been approved in combination with chemotherapy for the treatment of cervical cancer and ovarian cancer.

Current National Comprehensive Cancer Network (NCCN) guidelines support the use of bevacizumab in a variety of cancers including metastatic breast cancer, cervical cancer, CNS cancer, colorectal cancer, kidney cancer, mesothelioma, non-small cell lung cancer, ovarian cancer, soft tissue sarcoma, and uterine cancer.

POSITION STATEMENT:

NOTE: For ophthalmic indications, please refer to MCG # 09-J1000-78, Vascular Endothelial Growth Factor Inhibitors of Ocular Neovascularization.

I. Initiation of bevacizumab (Avastin®) meets the definition of medical necessity when used to treat the indications listed in Table 1, ALL of the indication-specific criteria are met, and the dose does not exceed either of the following:

1. 10 mg/kg every 2 weeks

2. 15 mg/kg every 3 weeks

Table 1

Indications and Specific Criteria

Indication

Criteria

Breast Cancer

ALL of the following:

1. Member’s disease is recurrent or metastatic

2. Member’s disease is HER2-negative

3. Member meets ONE of the following:

a. Member’s disease is progressive with no clinical benefit after three consecutive endocrine therapy regimens

b. Member has symptomatic visceral disease or visceral crisis

4. Bevacizumab is used in combination with paclitaxel

Cervical Cancer

BOTH of the following:

1. Member’s disease is persistent, recurrent, or metastatic

2. Bevacizumab will be used as first line therapy in combination with paclitaxel and ONE of the following:

i. cisplatin

ii. carboplatin

iii. topotecan

CNS Cancer

When the member is diagnosed with ANY of the following

1. Intracranial and/or spinal ependymoma (excludes subependymoma)

2. Anaplastic glioma

3. Glioblastoma

Colon and Rectal Cancer (also includes anal adenocarcinoma, appendiceal adenocarcinoma, and small bowel adenocarcinoma)

BOTH of the following:

1. Member has ONE of the following:

a. Metastatic disease

b. Unresectable or medically inoperable advanced disease

2. Bevacizumab will be used as a component of one of the following regimens

a. FOLFOX (fluorouracil, leucovorin, oxaliplatin)

b. FOLFIRI (fluorouracil, leucovorin, irinotecan)

c. CapeOX (capecitabine and oxaliplatin)

d. FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan)

e. Irinotecan

f. Capecitabine

g. 5-FU/LV (fluorouracil and leucovorin)

Kidney Cancer

BOTH of the following:

1. Member has relapsed or surgically unresectable stage IV disease

2. ANY of the following:

a. Bevacizumab will be used in combination with interferon alfa-2 as first line therapy in persons with predominant clear cell histology

b. Bevacizumab will be used as a single agent in persons with non-clear cell histology

Mesothelioma

When used in combination with pemetrexed and cisplatin on day 1 followed by single-agent maintenance therapy

Non-small cell lung cancer (NSCLC)

BOTH of the following:

1. Member’s NSCLC histology is non-squamous cell

2. Member’s disease is recurrent or metastatic

Ovarian Cancer (includes epithelial, fallopian tube, primary peritoneal, and malignant sex cord-stromal tumors)

When used to treat recurrent or persistent disease

Radiation necrosis of the brain

BOTH of the following:

1. Member is symptomatic

2. Member’s disease is refractory to corticosteroids

Soft-tissue sarcoma (STS)

ONE of the following:

1. Used as a single agent for angiosarcoma

2. Used in combination with temozolomide (Temodar) for treatment of solitary fibrous tumor/hemangiopericytoma

Uterine Neoplasm

When used as monotherapy in members who have progressed on prior cytotoxic chemotherapy.

CNS, central nervous system

Approval Duration: 180 days

II. Bevacizumab meets the definition of medical necessity when used for ANY of the following designated Orphan Drug indications (http://www.fda.gov/orphan/designat/list.htm) and the dose does not exceed the maximum FDA-approved dose:

1. In combination with a platinum and 5-FU or capecitabine for the treatment of stomach cancer.

2. Treatment of pancreatic cancer.

3. Treatment of melanoma stages IIb through IV as part of a combination chemotherapy regimen.

Approval Duration: 1 year

III. Continuation of bevacizumab meets the definition of medical necessity for the indications in Table 1 and designated orphan drug indications above when ALL of the following criteria are met:

a. The member has been previously approved by Florida Blue or another healthplan in the past 2 years, OR the member has previously met all indication-specific criteria

b. The dose does not exceed EITHER of the following:

1. 10 mg/kg every 2 weeks

2. 15 mg/kg every 3 weeks

Approval duration: 1 year

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: the FDA-approved indications and dosing for bevacizumab are identified in Table 2. Bevacizumab should be administered as an intravenous (IV) infusion. The first infusion should be administered over 90 minutes. If the first infusion is tolerated, the second infusion can be administered over 60 minutes; subsequent infusions can be administered over 30 minutes if the second infusion over 60 minutes is tolerated.

Table 2

FDA-approved indications and dosing

Indication

Dosage Regimen

Metastatic Colorectal Cancer

5 mg/kg every 2 weeks with bolus irinotecan/5-FU/leucovorin

10 mg/kg every 2 weeks with 5-FU/leucovorin/oxaliplatin

5 mg/kg every 2 weeks or 7.5 mg every 3 weeks with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy after progression on first line bevacizumab containing regimen

Non-squamous NSCLC

15 mg/kg every 3 weeks with carboplatin/paclitaxel

Glioblastoma

10 mg/kg every 2 weeks

Metastatic RCC

10 mg/kg every 2 weeks with interferon alfa

Persistent, recurrent, or metastatic carcinoma of the cervix

15 mg/kg IV every 3 weeks with paclitaxel/cisplatin or paclitaxel/topotecan

Platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer

10 mg/kg IV every 2 weeks with paclitaxel, pegylated liposomal doxorubicin or weekly topotecan

15 mg/kg IV every 3 weeks with topotecan given every 3 weeks

Platinum-sensitive recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer

15 mg/kg IV every 3 weeks with carboplatin/paclitaxel for 6 to 8 cycles followed by 15 mg/kg every 3 weeks as a single agent

15 mg/kg IV every 3 weeks with carboplatin/gemcitabine for 6 to 10 cycles followed by 15 mg/kg every 3 weeks as a single agent

Bevacizumab should be administered as an intravenous (IV) infusion; do not administer as an IV bolus or push

NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma

Dose modifications: there are no recommended dose reductions for bevacizumab. Bevacizumab should be discontinued in the following clinical situations:

• Gastrointestinal perforations (gastrointestinal perforations, fistula formation in the gastrointestinal tract, intra-abdominal abscess), fistula formation involving an internal organ

• Wound dehiscence and wound healing complications requiring medical intervention

• Serious hemorrhage (i.e., requiring medical intervention)

• Severe arterial thromboembolic events

Life-threatening (Grade 4) venous thromboembolic events, including pulmonary embolism

• Hypertensive crisis or hypertensive encephalopathy

Posterior Reversible Encephalopathy syndrome (PRES)

• Nephrotic syndrome

Bevacizumab should be temporarily suspended in the following clinical situations:

• At least 4 weeks prior to elective surgery

• Severe hypertension not controlled with medical management

• Moderate to severe proteinuria pending further evaluation

• Severe infusion reactions

Drug Availability: bevacizumab is supplied as a 100 mg/4 mL single-use vial and a 400 mg/16 mL single use vial.

PRECAUTIONS:

Boxed Warning

• Gastrointestinal Perforation: Occurs in up to 3.2% of bevacizumab-treated individuals. Discontinue bevacizumab for gastrointestinal perforation.

• Surgery and Wound Healing Complications: Discontinue in persons with wound dehiscence. Discontinue at least 28 days prior to elective surgery. Do not initiate bevacizumab for at least 28 days after surgery and until the surgical wound is fully healed.

• Hemorrhage: Severe or fatal hemorrhage, hemoptysis, gastrointestinal bleeding, CNS hemorrhage, and vaginal bleeding are increased in bevacizumab- treated individuals. Do not administer bevacizumab to individuals with serious hemorrhage or recent hemoptysis.

Precautions/Warnings:

Perforation or Fistula Formation: Discontinue bevacizumab if perforation or fistula formation occurs.

• Arterial Thromboembolic Events (ATE) (e.g., myocardial infarction, cerebral infarction): Discontinue bevacizumab for severe ATE.

Venous Thromboembolic Events: Discontinue bevacizumab for life-threatening events.

• Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend bevacizumab if not medically controlled. Discontinue bevacizumab for hypertensive crisis or hypertensive encephalopathy.

Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue bevacizumab.

• Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome. Temporarily suspend bevacizumab for moderate proteinuria.

• Infusion Reactions: Stop for severe infusion reactions.

Embryo-fetal toxicity: Advise females of potential risk to a fetus and the need for use of effective contraception.

• Ovarian Failure: Inform females of reproductive potential of the risk of ovarian failure with bevacizumab.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

C9257

Injection, bevacizumab, 0.25 mg

J9035

Injection, bevacizumab, 10mg

ICD-10 Diagnoses Codes That Support Medical Necessity:

C16.0 – C16.9

Malignant neoplasm of stomach

C17.0

Malignant neoplasm of duodenum

C17.1

Malignant neoplasm of jejunum

C17.2

Malignant neoplasm of ileum

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0 – C18.9

Malignant neoplasm of colon

C19 – C20

Malignant neoplasm of rectosigmoid junction and rectum

C21.0 - C21.8

Malignant neoplasm of anus and anal canal

C25.0 – C25.9

Malignant neoplasm of pancreas

C33 – C34.92

Malignant neoplasm of trachea, bronchus and lung

C38.4

Malignant neoplasm of pleura

C43.0 – C43.9

Malignant melanoma of skin

C45.0

Mesothelioma of pleura

C47.8

Malignant neoplasm of overlapping sites of peripheral nerves and autonomic nervous system

C48.0

Malignant neoplasm of retroperitoneum

C48.1

Malignant neoplasm of specified parts of peritoneum

C48.2

Malignant neoplasm of peritoneum, unspecified

C48.8

Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

C49.0 – C49.9

Malignant neoplasm of connective and soft tissue

C50.011 – C50.929

Malignant neoplasm of breast

C53.0 – C53.9

Malignant neoplasm of endocervix, exocervix, overlapping sites of cervix uteri, unspecified cervix uteri

C54.1 – C54.3

Malignant neoplasm of endometrium, myometrium, and fundus uteri

C54.9

Malignant neoplasm of corpus uteri, unspecified

C56.1 – C57.9

Malignant neoplasm of ovary and other and unspecified female genital organs

C64.1 C64.9

Malignant neoplasm of unspecified kidney, except renal pelvis

C65.1 C65.9

Malignant neoplasm of unspecified renal pelvis

C71.0 – C71.9

Malignant neoplasm of brain

C72.9

Malignant neoplasm of central nervous system, unspecified

C78.00 – C78.02

Secondary malignant neoplasm of unspecified lung

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

D43.0 – D43.2

Neoplasm of uncertain behavior of brain, unspecified

D43.4

Neoplasm of uncertain behavior of spinal cord

D49.2

Neoplasm of unspecified behavior of bone, soft tissue, and skin

T66.XXXA

Radiation sickness, unspecified, initial encounter

T66.XXXD

Radiation sickness, unspecified, subsequent encounter

T66.XXXS

Radiation sickness, unspecified, sequela

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

DEFINITIONS:

None.

RELATED GUIDELINES:

Gemcitabine (Gemzar®), 09-J0000-96
Irinotecan HCl (Camptosar®) IV, 09-J0000-99

Tumor Markers, 05-86000-22

Vascular Endothelial Growth Factor Inhibitors of Ocular Neovascularization, 09-J1000-78

Verteporfin (Visudyne™) Injection, 09-J1000-72

OTHER:

None applicable.

REFERENCES:

  1. Avastin (bevacizumab) [package insert]. Genentech, Inc. South San Francisco (CA): December 2016.
  2. Bevacizumab. In McEvoy GK, editor. AHFS drug information 2017 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2016 [cited 2017 May 22].
  3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017 May 22]. Available from: http://www.clinicalpharmacology.com/.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015-06-13]. Available from: http://clinicaltrials.gov/.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 May 22]. Available from: http://www.thomsonhc.com/.
  6. Furuse M, Nonoguchi N, Kuroiwa T et al. A prospective, multicenter, single-arm clinical trial of bevacizumab for patients with surgically untreatable, symptomatic brain radiation necrosis. Neurooncol Pract. 2016; 3(4):272-280.
  7. Ingenix HCPCS Level II, Expert 2013.
  8. Ingenix ICD-9-CM for Physicians – Volumes 1 & 2, Expert 2013.
  9. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 2017 May 30]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  10. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Anal Carcinoma. Version 1.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/anal.pdf Accessed 12/09/16.
  11. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Breast Cancer. Version 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf Accessed 5/20/16.
  12. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Central Nervous System Cancers. Version 1.2016. Available at http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf Accessed 5/31/17.
  13. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Cervical Cancer. Version 1.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/cervical.pdf Accessed 5/31/17.
  14. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Colon Cancer. Version 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf Accessed 5/31/17.
  15. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Kidney Cancer. Version 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf Accessed 5/31/17.
  16. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Malignant Pleural Mesothelioma. Version 1.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/mpm.pdf Accessed 5/31/17.
  17. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Non-small cell lung cancer. Version 6.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf Accessed 5/31/17.
  18. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 1.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf Accessed 5/31/17.
  19. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Rectal Cancer. Version 3.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/rectal.pdf Accessed 5/31/17.
  20. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Soft Tissue Sarcoma. Version2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/sarcoma.pdf Accessed 5/31/17.
  21. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Uterine Neoplasms. Version 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/uterine.pdf Accessed 5/31/17.
  22. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 May 30]. 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 Coverage Committee on 06/14/17.

GUIDELINE UPDATE INFORMATION:

11/15/06

New Medical Coverage Guideline.

07/15/07

Reviewed guideline: Maintain current coverage and limitations. Reformatted guideline, renamed putting generic first, and references.

07/15/08

Reviewed guideline with no change in coverage. Added statement regarding proper coding, added related guideline and updated references.

04/15/09

Review and revision of guideline; consisting of changing the name of the guideline, adding 5 new indications to the position statement, adding maximum dosing, updating references, and adding ICD-9 codes for cervical cancer.

10/01/09

Revision to guideline; consisting of updating maximum dosing description in Position statement, updating HCPCS coding and addition of 3 new diagnosis codes.

10/15/09

Revision to guideline; consisting of updating codes.

01/01/10

Annual HCPCS coding update: deleted HCPCS code Q2024.

01/15/10

Revision to guideline; consisting of updating coding.

04/15/10

Revision to guideline; consisting of updating coding.

08/01/10

Review and revision to guideline; consisting of updating ICD-9 coding, black box warning and references.

08/15/11

Review and revision to guideline; consisting of updating coding and references.

07/15/12

Revision to guideline; consisting of modifying dosage limitations.

08/15/12

Review and revision to guideline; consisting reformatting position statement, update precautions, coding, program exceptions and references.

12/15/12

Revision to guideline; consisting of removing ophthalmologic indications and referencing MCG# 09-J1000-78, Vascular Endothelial Growth Factor Inhibitors of Ocular Neovascularization.

04/15/13

Revision to guideline; consisting of adding new indication to position statement.

08/15/13

Review and revision to guideline; consisting of revising description section, revising and reformatting position statement, dosage/administration, and precautions sections; updating references, program exceptions and coding.

08/15/14

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

10/15/14

Revision to guideline; consisting of revising position statement.

11/15/14

Revision to guideline; consisting of position statement.

08/15/15

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

11/01/15

Revision: ICD-9 Codes deleted.

07/15/16

Review and revision to guideline; consisting of revising position statement; updating dosing, warnings, coding and references.

01/15/17

Revision to guideline; consisting of updating position statement, coding and references.

07/15/17

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

Date Printed: October 20, 2017: 08:41 AM