Effective Date: 06/01/2011
Title: Bevacizumab (biosimilar products and Avastin)
Revision Date: 04/01/2020
CPT Code(s): C9257, J9035,Q5107, Q5118
This policy will apply to
all services performed on or after the above revision date which will become the
new effective date.
For all services referred
to in this policy that were performed before the revision date, contact customer
service for the rules that would apply.
(both Avastin and biosimilar products) is an intravenous medication used to
treat certain advanced cancers. It
is also used in a low-dose form to treat age related macular degeneration.
(both Avastin and biosimilar products) requires pre-authorization when used to
treat cancer. For patients starting therapy, a biosimilar product must be tried
first before brand name Avastin would be approved.
Bevacizumab is not
covered for more than one line of therapy for any cancer (except colorectal
Bevacizumab may be added
later to approved combinations if the patient is recovering from a surgical
procedure. Coverage is allowed if the drug is added within 90 days of the start
On November 18, 2011, the
FDA revoked the agency’s approval of the breast cancer indication for Avastin
(bevacizumab) after concluding that the drug has not been shown to be safe and
effective for that use.
High-dose bevacizumab may
be used on an emergency basis to stop severe, intractable bleeding that has not
responded to other measures—only for patients with an inherited syndrome called
Hereditary Hemorrhagic Telangiectasia (HHT).
requires pre-authorization when used to prevent severe, recurrent bleeding for
patients with HHT.
(bevacizumab, 0.25 mg) is eligible for coverage through the specialty pharmacy
program for neovascular (“wet”) age related macular degeneration.
(both Avastin and biosimilar products), 10 mg is
considered medically necessary for treatment of cancers under the following
criteria. For new patients starting
therapy on bevacizumab, a biosimilar product must be tried first before brand
name Avastin would be approved.
Adult intracranial or
spinal ependymoma: as treatment for
disease progression after radiation therapy or recurrence
Anaplastic glioma or
glioblastoma: as treatment for recurrent disease or salvage therapy
persistent, recurrent, or
metastatic cervical cancer AND
Being used in combination
with paclitaxel and cisplatin or topotecan
First or second line
treatment for advanced or metastatic disease
Neoadjuvant or adjuvant
therapy for patients with resectable or unresectable liver and/or lung
cell lung cancer:
First-line therapy for
unresectable, locally advanced, recurrent, or metastatic disease in patients
with performance status 0-1 with no history of hemoptysis
therapy in patients who achieve tumor response or stable disease after
first-line treatment that included Avastin
Second line therapy for
progression in patients with multiple symptomatic systemic lesions in
combination with platinum doublet therapy
For clinical relapse in
patients with stage II-IV granulosa cell tumors
For progressive or
persistent disease on primary chemotherapy or relapse after complete remission
in patients with stage II-IV epithelial/fallopian tube/primary peritoneal
For primary treatment for
patients with suspected unresectable residual disease
for primary adjuvant
treatment for stage II-IV disease
Soft tissue sarcoma:
Angiosarcoma as a single
Solitary fibrous tumor or
hemangiopericytoma in combination with temozolomide
Single agent therapy for
disease that has progressed on prior cytotoxic chemotherapy
(both Avastin and biosimilar products) may be used on an emergency basis to stop
severe, intractable bleeding that has not responded to other measures—only for
patients with an inherited syndrome called Hereditary Hemorrhagic Telangiectasia
(both Avastin and biosimilar products) requires
pre-authorization when used to prevent severe, recurrent bleeding for patients
High-dose bevacizumab (both Avastin and biosimilar products)
is considered medically necessary for
prevention of bleeding in patients with HHT when the following criteria are met:
Definite confirmation of HHT diagnosis
through genetic testing or consensus clinical criteria (at least 3 out of the
following 4—spontaneous, recurrent episodes of epistaxis; multiple
telangiectasias at characteristic sites; visceral telangiectasias or
arteriovenous malformations and family history of a first degree relative with
confirmed HHT) with EITHER
Hemoglobin levels < 8
despite 3 months of adequate treatment with intravenous
iron products OR
More than three
documented episodes of severe epistaxis or gastrointestinal bleeding requiring
treatment in an ER or inpatient hospital setting.
Used In This BI:
INJECTION BEVACIZUMAB-AWWB BIOSIMILAR (Mvasi) 10 MG
Injection, bevacizumab-bvzr, biosimilar (Zirabev), 10mg
High-dose Bevacizumab injection (Avastin), 10 mg
Low-dose Bevacizumab injection, 0.25mg
Avastin (bevacizumab) is considered experimental and investigational for
treatment of other cancers.
Bevacizumab is a recombinant humanized monoclonal antibody to vascular
endothelial growth factor (VEGF). It is designed to bind to and inhibit VEGF,
which plays an important role in tumor angiogenesis, a process critical for
tumor growth and metastasis. On February 26, 2004, the U.S. Food and Drug
Administration (FDA) approved bevacizumab (Avastin) (Genentech, Inc., South San
Francisco, CA) for use in combination with intravenous 5-FU based chemotherapy
as a first-line treatment for patients with metastatic colorectal cancer. It is
the first FDA-approved therapy designed to inhibit angiogenesis. Bevacizumab is
administered intravenously. In clinical trials, the most common side effects
associated with the use of bevacizumab were asthenia, pain, abdominal pain,
headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis,
constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative
dermatitis, and proteinuria. The most serious adverse events were
gastrointestinal perforations/wound healing complications, hemorrhage,
hypertensive crises, nephrotic syndrome, and congestive heart failure.
Preliminary results from a National Cancer Institute-sponsored multicenter
randomized controlled clinical trial conducted by the Eastern Cooperative
Oncology Group (ECOG) of 722 women with previously untreated recurrent or
metastatic breast cancer show that women who received bevacizumab in combination
with paclitaxel had a statistically significant increase in progression-free
survival of four months than women who received paclitaxel alone. The data
monitoring committee overseeing the trial recommended that the results of a
recent interim analysis be made public because the study had met its primary
endpoint of increasing progression-free survival. Women whose tumors
over-expressed HER-2 were not included in the study unless they had previously
received trastuzumab (Herceptin) or were unable to receive trastuzumab. Also
excluded were women who had received preventive chemotherapy treatment with
paclitaxel within the previous 12 months, as well as women with a prior history
of thrombosis or who were on anticoagulants. Serious hemorrhage and thrombosis
were rare in this study. Women receiving the combination of paclitaxel and
bevacizumab had small increases in rates of neuropathy, hypertension, and
proteinuria than women receiving paclitaxel alone. Other side effects were
similar between the two treatment groups.
previous Phase III study of bevacizumab in metastatic breast cancer found that
the addition of bevacizumab to capecitabine produced a significant increase in
response rates, but this did not translate into improved progression free
survival or overall survival (Miller, et al., 2005). This randomized phase III
trial compared the efficacy and safety of capecitabine with or without
bevacizumab in 462 patients with metastatic breast cancer previously treated
with an anthracycline and a taxane. Patients were randomly assigned to receive
capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks,
alone or in combination with bevacizumab (15 mg/kg) on day 1. Combination
therapy significantly increased the response rates (19.8% v 9.1%; P = .001);
however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio =
0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in
quality of life as measured by the Functional
Assessment of Cancer Treatment-Breast were comparable in both treatment groups.
The investigators reported that bevacizumab was well tolerated in this heavily
pretreated patient population (Miller, et al., 2005). No significant
differences were found in the incidence of diarrhea, hand-foot syndrome,
thromboembolic events, or serious bleeding episodes between treatment groups. Of
other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9%
v 0.5%) was more frequent in patients receiving bevacizumab.
NOTE: In December 2010, the FDA recommended removal of the breast cancer
indication from the product labeling. This recommendation came after reviewing
the results of four clinical studies of bevacizumab in women with breast cancer
and determining that the data indicate that the drug does not prolong overall
survival in breast cancer patients or provide a sufficient benefit in slowing
disease progression to outweigh the significant risk to patients (see Adverse
Reactions). Under the accelerated approval process, Genentech has the
opportunity to request a hearing to appeal this decision. If the appeal is
unsuccessful, the indication will be removed.
NOTE: On November 18, 2011, The FDA revoked the agency’s approval of the breast
cancer indication for Avastin (bevacizumab) after concluding that the drug has
not been shown to be safe and effective for that use.
Hereditary Hemorrhagic Telangiectasia (HHT) is an inherited genetic disorder
(also known as Osler-Weber-Rendu syndrome) that affects the formation of blood
vessels. Depending on the population studied, the prevalence is about 1 in
5,000 to 1 in 10,000 people. While there are genetic tests that can confirm the
diagnosis, the diagnosis is more commonly made using consensus clinical
criteria. Complications of HHT are usually caused by bleeding from malformed
blood vessels. Recurrent epistaxis is seen in 75% of patients and recurrent
gastrointestinal bleeding affects 25% of patients with HHT. Aside from requiring
emergency interventions, these recurrent episodes of bleeding often lead to
significant anemia requiring iron therapy or blood transfusions. The presence
of visceral arteriovenous malformations can sometimes lead to catastrophic
Elevated blood levels of vascular endothelial growth factor (VEGF) play a role
in stimulating abnormal growth of blood vessels in patients with HHT. By
attaching to VEGF, bevacizumab (Avastin) can decrease the growth of abnormal
blood vessels in patients with HHT and has been shown to reduce or prevent some
of the complications.
Comprehensive Cancer Network Drugs and Biologics Compendium. Accessed
Naim R, et al. Patients with hereditary
hemorrhagic telangiectasia have increased plasma levels of vascular endothelial
growth factor and transforming growth factor-β1 as well as high ALK1 tissue
expression. Haematologica 2005; 90:818-828.
Fischbach W. Dramatic improvement in
hereditary hemorrhagic telangiectasia after treatment with the vascular
endothelial growth factor (VEGF) antagonist bevacizumab.
Ann Hematol 2006; 85:631-632.
vanden Driesen R,
Delriviere L. Bevacizumab reverses need
for liver transplantation in hereditary hemorrhagic telangiectasia.
Liver Transpl 2008;14:210-213
Jee Wan Wee, Young Woo Jeon, Jun Young Eun, Han Jo Kim, Sang
Byung Bae, Kyu Taek Lee. . (2014) hereditary hemorrhagic telangiectasia treated
with low dose intravenous bevacizumab. Blood Research
Wenhao Li, Sreelakshmi Kotha, Deepak Joshi. . (2017) Upper
Gastrointestinal Bleeding Caused by Hereditary Hemorrhagic Telangectasia.
Clinical Gastroenterology and Hepatology
L. Robard et al. Guidelines of the French Society of
Otorhinolaryngology (SFORL) (short version). Specific treatment of epistaxis in
Rendu-Osler-Weber disease. European Annals of
Otorhinolaryngology, Head, and Neck Diseases. 2017; 134:1, 37-41.
Narendranath Epperla, Jonathan T. Kapke, Matthew Karafin, Kenneth
D. Friedman, Patrick Foy. . (2016) Effect of systemic bevacizumab in severe
hereditary hemorrhagic telangiectasia associated with bleeding.
American Journal of Hematology 91:6,
Natalia P. Arizmendez, Luke Rudmik, David M. Poetker. . (2015)
Intravenous bevacizumab for complications of hereditary hemorrhagic
telangiectasia: a review of the literature.
International Forum of Allergy & Rhinology 5:10.1002/alr.2015.5.issue-11,
Alderman, Jonathan Corlett, Jonathan Cullis. . (2013) the treatment of recurrent
epistaxis due to hereditary haemorrhagic telangiectasia with intranasal
bevacizumab. British Journal of Haematology
Lupu, Carmen Stefanescu, Xavier Treton, Alain Attar, Olivier Corcos, Yoram
Bouhnik. . (2013) Bevacizumab as Rescue Treatment for Severe Recurrent
Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia.
Journal of Clinical Gastroenterology 47,
Karnezis, Terence M. Davidson. . (2011) Efficacy of intranasal bevacizumab (Avastin)
treatment in patients with hereditary hemorrhagic telangiectasia-associated
epistaxis. The Laryngoscope 121,
Brinkerhoff, Brian T., Poetker, David M., Choong, Nicholas W.,. . (2011)
Long-Term Therapy with Bevacizumab in Hereditary Hemorrhagic Telangiectasia.
New England Journal of Medicine 364:7,
Application to Products
This policy applies to all health plans administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet. Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) for those plans insured by QualChoice. In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC, the SPD or EOC, as applicable, will prevail. State and federal mandates will be followed as they apply.
Changes: QualChoice reserves the right to alter, amend, change or supplement benefit interpretations as needed.