Medical Policy

Policy Num: 05.001.017
Policy Name: Bevacizumab
Policy ID: [05.001.017] [Ac / L / M+ / P+] [0.00.00]

Last Review: October 24, 2024
Next Review: October 20, 2025

Related Policies: None

Bevacizumab

Popultation Reference No.	Populations	Interventions	Comparators	Outcomes
1	Individuals: With colorectal cancer (CRC)	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
2	Individuals: With non-squamous non-small cell lung cancer (NSCLC)	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
3	Individuals: With cervical cancer	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
4	Individuals: With renal cell carcinoma (RCC)	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
5	Individuals: With central nervous system (CNS) cancer	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
6	Individuals: With ovarian cancer	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
7	Individuals: With soft tissue sarcoma	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
8	Individuals: With endometrial carcinoma	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
9	Individuals: With malignant pleural mesothelioma	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
10	Individuals: With vulvar cancer	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
11	Individuals: With small bowel adenocarcinoma	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome
12	Individuals: With hepatocellular carcinoma (HCC)	Interventions of interest are: Treatment with bevacizumab	Comparators of interest are: Oncologic treatment w/o bevacizumab	Relevant outcomes include: Prevent tumor growth Prevent metastasis Improve life expectancy improve the net health outcome

Summary

Bevacizumab is a humanized monoclonal antibody directed against Vascular Endothelial Growth Factor A (VEGF-A). Vascular Endothelial Growth Factors (VEGF) and their receptors (VEGF-R) contribute to the tumor growth and to the metastasis through the promotion of the angiogenesis.

Objective

The objective of this evidence review is to determine whether bevacizumab improves the net health outcome in patients with need of oncologic treatment.

Policy Statements

The use of bevacizumab is considered medically necessary for the following conditions:

I. FDA-approved indications:

Cervical cancer - in combination with paclitaxel and cisplatin or topotecan for persistent, recurrent, or metastatic disease
Cervical cancer - in combination with pembrolizumab and chemotherapy for persistent, metastatic, or recurrent disease with PD-L1 combined positive score ≥ 1
CNS - Brain cancer (glioblastoma) - as a single agent or in combination with carmustine, temozolomide, or lomustine in patients with recurrent disease
Colon cancer - in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment of metastatic disease
Colon cancer - in combination with fluoropyrimidine-irinotecan-, or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment of metastatic disease in patients who have progressed on a first-line bevacizumab- or bevacizumab biosimilar-containing regimen
Hepatocellular carcinoma - in combination with atezolizumab in patients with unresectable or metastatic disease who have not received prior systemic therapy
Non-small cell lung cancer - in combination with carboplatin and paclitaxel for first-line treatment of non-squamous, unresectable, locally advanced, recurrent, or metastatic disease
Ovarian cancer - for the treatment of recurrent epithelial disease in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant disease or in combination with carboplatin and paclitaxel or carboplatin and gemcitabine followed by single agent bevacizumab for platinum-sensitive disease
Ovarian cancer - in combination with carboplatin and paclitaxel followed by single agent bevacizumab for stage III-IV disease following initial surgical resection
Rectal cancer - in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment of metastatic disease
Rectal cancer - in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab- or bevacizumab biosimilar-containing regimen

II. Bevacizumab is recommended by the NCCN Drugs and Biologics Compendium^® for off-label use for the following indications and considered medically necessary :

Ampullary adenocarcinoma - as first-line therapy for intestinal type disease in combination with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan), FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), or CapeOx (capecitabine and oxaliplatin) for unresectable localized disease, stage IV resected disease, or metastatic disease at initial presentation in patients with performance status 0 - 1; and in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOx (capecitabine and oxaliplatin), capecitabine, or fluorouracil and leucovorin in patients with performance status 2
Ampullary adenocarcinoma - as subsequent therapy for disease progression for intestinal type disease in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) for patients with performance status 0 - 1, and in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOx (capecitabine and oxaliplatin), capecitabine, or fluorouracil and leucovorin in patients with performance status 2
Appendiceal adenocarcinoma - as initial systemic therapy for advanced or metastatic disease that is proficient mismatch repair/microsatellite-stable [pMMR/MSS] or deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H]) when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), FOLFIRI (fluorouracil, leucovorin and irinotecan), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), 5-FU/LV (fluorouracil and leucovorin), or capecitabine
Appendiceal adenocarcinoma - as subsequent therapy for progression of advanced or metastatic disease that is proficient mismatch repair/microsatellite-stable [pMMR/MSS] or deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H]) when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy in combination with irinotecan with or without oxaliplatin, FOLFIRI (fluorouracil, leucovorin and irinotecan), FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), or trifluridine and tipiracil
Cervical cancer - as first-line therapy in combination with paclitaxel and carboplatin for squamous cell carcinoma, adenosquamous, or adenocarcinoma with local/regional recurrence or stage IVB disease or disease with distant metastases
Cervical cancer - as second-line or subsequent therapy in combination with paclitaxel and carboplatin for squamous cell carcinoma, adenosquamous, or adenocarcinoma with local/regional recurrence or stage IVB disease or disease with distant metastases, if not used previously as first-line therapy
Cervical cancer - as single agent second-line or subsequent therapy for squamous cell carcinoma, adenosquamous, or adenocarcinoma with local/regional recurrence or stage IVB disease or disease with distant metastases
Cervical cancer - as single agent second-line or subsequent therapy for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC)
CNS - Brain cancer (astrocytoma or oligodendroglioma) - as a single agent or in combination with carmustine, temozolomide, or lomustine for recurrent disease; or as short course, single agent therapy for the management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect
CNS - Brain cancer (glioblastoma) - as short course, single agent therapy for the management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect
CNS - Brain cancer (glioma, medulloblastoma, or metastatic spine tumors) - as short course, single agent therapy for the management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect
CNS - Brain cancer (meningioma) - as short course, single agent therapy for the management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect, or as a single agent or in combination with everolimus for patients with surgically inaccessible recurrent or progressive disease when radiation therapy is not possible
CNS - Brain metastases (limited or extensive) - as short-course single agent therapy for the management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect
CNS - Intracranial and spinal ependymoma (excluding subependymoma) - as a single agent for progression or recurrent disease in patients who are refractory to surgery or radiation therapy, if received prior radiation therapy and had gross total or subtotal resection with negative cerebrospinal fluid (CSF) cytology, subtotal resection and evidence of metastases (brain, spine, or CSF), or unresectable disease
CNS - Intracranial and spinal ependymoma (excluding subependymoma) - as short-course, single agent therapy for the management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect
CNS - Primary CNS lymphoma - as short-course, single agent therapy for management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect
Colon cancer - as primary treatment in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin and irinotecan), CapeOx (capecitabine and oxaliplatin), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), 5-FU/LV (fluorouracil and leucovorin), or capecitabine for locally unresectable or medically inoperable proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy
Colon cancer - as adjuvant treatment in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOx (capecitabine and oxaliplatin), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), 5-FU/LV (fluorouracil and leucovorin), or capecitabine for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy following synchronized or staged resection and/or local therapy for synchronous liver and/or lung metastases that converted from unresectable to resectable disease after primary treatment, following resection and/or local therapy for resectable metachronous metastases in patients who have received previous chemotherapy, or for unresectable metachronous metastases that converted to resectable disease after initial treatment
Colon cancer - as adjuvant treatment in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOx (capecitabine and oxaliplatin), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), 5-FU/LV (fluorouracil and leucovorin), or capecitabine for deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease following resection and/or local therapy for resectable metachronous metastases and received previous immunotherapy
Colon cancer - as adjuvant treatment in combination with irinotecan for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy for unresectable metachronous metastases that converted to resectable disease after primary treatment
Colon cancer - as primary treatment in combination with CapeOx (capecitabine and oxaliplatin) or FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease for unresectable synchronous liver and/or lung metastases
Colon cancer - as primary treatment in combination with CapeOx (capecitabine and oxaliplatin), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), or capecitabine for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy for synchronous abdominal/peritoneal metastases, unresectable synchronous metastases of other sites, or for unresectable metachronous metastases in patients who have not received previous FOLFOX or CapeOx therapy within the past 12 months and have had previous 5-FU/LV (fluorouracil and leucovorin) or capecitabine therapy or who have not had previous chemotherapy
Colon cancer - as primary treatment in combination with irinotecan for proficient mismatch repair/microsatellite-stable (pMMR/MSS) unresectable metachronous metastases in patients who have had previous FOLFOX or CapeOx therapy within the past 12 months
Colon cancer - as subsequent treatment for disease progression in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), irinotecan with or without oxaliplatin, or trifluridine and tipiracil for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy
Diffuse high-grade glioma (Pediatric) - single agent, palliative treatment for recurrent or progressive disease in patients who do NOT have a diagnosis of oligodendroglioma, IDH-mutant and 1p/19q co-deleted or astrocytoma IDH-mutant
Endometrial cancer (serous carcinoma, clear cell carcinoma, undifferentiated/dedifferentiated carcinoma, and carcinosarcoma) - in combination with carboplatin and paclitaxel as first-line therapy for advanced and recurrent disease or as second-line and subsequent therapy for advanced and recurrent disease when bevacizumab or a bevacizumab biosimilar in combination with paclitaxel was not previously used
Endometrial cancer (serous carcinoma, clear cell carcinoma, undifferentiated/dedifferentiated carcinoma, and carcinosarcoma) - as a single agent, second-line or subsequent therapy for disease that progressed on prior cytotoxic chemotherapy
Hepatocellular carcinoma - in combination with atezolizumab as first-line treatment for Child Pugh class A or B, unresectable disease in patients who are not candidates for transplant; liver-confined disease, inoperable by performance status, comorbidity, or with minimal or uncertain extrahepatic disease; or metastatic disease or extensive liver tumor burden
Mesothelioma: Peritoneal - as first-line systemic therapy in combination with pemetrexed and cisplatin or, for non-candidates for cisplatin, pemetrexed and carboplatin for diffuse disease with unicavitary, epithelioid histology; for diffuse disease with biphasic/sarcomatoid histology or bicavitary disease; or for recurrence of benign multicystic or well-differentiated papillary disease after prior cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy
Mesothelioma: Peritoneal - as subsequent systemic therapy in combination with atezolizumab, pemetrexed and cisplatin, or (in non-candidates for cisplatin) pemetrexed and carboplatin
Mesothelioma: Pleural - as first-line systemic therapy or induction chemotherapy in combination with pemetrexed and cisplatin or pemetrexed and carboplatin (if not a candidate for cisplatin) for clinical stage I-IIIA disease with epithelioid histology or for clinical stage IIIB or IV disease, sarcomatoid or biphasic histology, or medically inoperable tumors
Mesothelioma: Pleural - as subsequent therapy in combination with pemetrexed and cisplatin or pemetrexed and carboplatin (if not a candidate for cisplatin) when immunotherapy was administered as first-line treatment or when given as a rechallenge if good response to front-line pemetrexed-based treatment
Non-small cell lung cancer (NSCLC) - as first-line therapy for the treatment of stage IV or recurrent disease in combination with carboplatin and pemetrexed; cisplatin and pemetrexed; or atezolizumab, carboplatin, and paclitaxel
Non-small cell lung cancer (NSCLC) - as a single agent or in combination with pemetrexed or atezolizumab as continuation maintenance therapy for non-squamous, stage IV metastatic or recurrent disease
Non-small cell lung cancer (NSCLC) - as subsequent therapy for the treatment of stage IV or recurrent disease in combination with carboplatin and paclitaxel; carboplatin and pemetrexed; cisplatin and pemetrexed; or atezolizumab, carboplatin, and paclitaxel
Non-small cell lung cancer - in combination with erlotinib as first-line or initial therapy for EGFR mutation positive Stage IV, recurrent or advanced disease
Non-small cell lung cancer - as single agent therapy or in combination with pemetrexed or atezolizumab for continuation maintenance therapy when negative for actionable molecular markers and PD-L1 expression ‹ 1%
Ovarian cancer (epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer) – in combination with carboplatin and paclitaxel as neoadjuvant therapy; or in combination with carboplatin and paclitaxel or carboplatin and docetaxel as continued treatment for stable disease following neoadjuvant therapy in patients who are poor surgical candidates and have low likelihood of optimal cytoreduction
Ovarian cancer (malignant sex cord-stromal tumors) – as a single agent for persistent or recurrent disease in patients with clinical relapse and stage II-IV disease
Ovarian cancer (epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, mucinous carcinoma, grade 1 endometrioid carcinoma, low-grade serous carcinoma, carcinosarcoma, clear cell carcinoma) – as adjuvant therapy in combination with carboplatin and paclitaxel; carboplatin and docetaxel; fluorouracil, leucovorin, and oxaliplatin; or capecitabine and oxaliplatin in patients with pathologic stage II-IV disease
Ovarian cancer (epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, mucinous carcinoma, grade 1 endometrioid carcinoma, low-grade serous carcinoma, carcinosarcoma, clear cell carcinoma) – as a single agent or in combination with capecitabine and oxaliplatin; carboplatin and gemcitabine; carboplatin and liposomal doxorubicin; carboplatin and paclitaxel; fluorouracil, leucovorin, and oxaliplatin; ixabepilone; liposomal doxorubicin; mirvetuximab soravtansine-gynx; niraparib; oral cyclophosphamide; paclitaxel and carboplatin; topotecan; or weekly paclitaxel for persistent or recurrent disease
Ovarian cancer (epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, mucinous carcinoma, grade 1 endometrioid carcinoma, low-grade serous carcinoma, carcinosarcoma, clear cell carcinoma) – as single agent maintenance therapy in patients with partial or complete response following recurrence therapy with chemotherapy plus bevacizumab for platinum-sensitive disease; or as maintenance therapy in combination with olaparib in patients with stage II-IV disease with complete or partial response to primary therapy including bevacizumab or a bevacizumab biosimilar
Rectal cancer - as primary treatment for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOx (capecitabine and oxaliplatin), capecitabine, or 5FU-LV (fluorouracil and leucovorin) in patients with T3, N Any; T1-2, N1-2; T4, N Any disease; or locally unresectable or medically inoperable disease when resection is contraindicated following neoadjuvant therapy or total neoadjuvant therapy
Rectal cancer - as adjuvant treatment in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), 5FU-LV (fluorouracil and leucovorin), or capecitabine for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy following resection and/or local therapy for resectable metachronous metastases and received previous chemotherapy or for unresectable metachronous metastases that converted to resectable disease after initial or primary treatment
Rectal cancer - as adjuvant treatment in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), 5FU-LV (fluorouracil and leucovorin), or capecitabine for deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease following resection and/or local therapy for resectable metachronous metastases and received previous immunotherapy
Rectal cancer - as adjuvant treatment in combination with irinotecan for proficient mismatch repair/microsatellite-stable (pMMR/MSS) unresectable metachronous metastases that converted to resectable disease after initial or primary treatment
Rectal cancer - as primary treatment in combination with CapeOx (capecitabine and oxaliplatin), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), or capecitabine for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy for synchronous abdominal/peritoneal metastases, unresectable synchronous metastases of other sites, or unresectable isolated pelvic/anastomotic recurrence; or for unresectable metachronous metastases in patients who have not received adjuvant FOLFOX or CapeOx therapy within the past 12 months and have had previous 5FU-LV (fluorouracil and leucovorin) or capecitabine therapy or who have not had previous chemotherapy
Rectal cancer - as primary treatment in combination with CapeOx (capecitabine and oxaliplatin) or FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable
Rectal cancer - as initial treatment in combination with irinotecan for proficient mismatch repair/microsatellite-stable (pMMR/MSS) unresectable metachronous metastases in patients who have had previous FOLFOX or CapeOx therapy within the past 12 months
Rectal cancer - as subsequent treatment for disease progression in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), irinotecan with or without oxaliplatin, or trifluridine and tipiracil for proficient mismatch repair/microsatellite-stable (pMMR/MSS) or deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease when the patient is ineligible for or progressed on checkpoint inhibitor immunotherapy
Renal cell cancer – in combination with erlotinib for relapsed or stage IV, advanced papillary renal cell carcinoma (RCC), including hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated RCC
Renal cell cancer – as subsequent, single agent therapy for relapsed or stage IV, clear cell disease
Renal cell cancer – as a single agent or in combination with everolimus for relapsed or stage IV, non-clear cell disease
Small bowel adenocarcinoma - for advanced metastatic disease in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), CapeOx (capecitabine and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), or FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) when intensive therapy is recommended and in combination with capecitabine, 5-FU/leucovorin (fluorouracil and leucovorin), or FOLFIRI (fluorouracil, leucovorin, and irinotecan) when intensive therapy is not recommended
Soft tissue sarcoma - as a single agent for the treatment of angiosarcoma
Soft tissue sarcoma - in combination with temozolomide for the treatment of solitary fibrous tumor
Vulvar cancer – as first-line therapy in combination with cisplatin and paclitaxel or carboplatin and paclitaxel for locally advanced unresectable disease (larger T2, T3) or initially unresectable nodes regardless of T stage that is clinically positive for residual tumor at the primary site and/or nodes or for locally advanced disease (larger T2, T3) or initially unresectable nodes regardless of T stage with positive margins following resection
Vulvar cancer – as second-line or subsequent therapy in combination with cisplatin and paclitaxel or carboplatin and paclitaxel as additional treatment following primary therapy with concurrent chemoradiation; as primary treatment for metastatic disease beyond the pelvis (any T, any N, M1 beyond pelvis); for isolated inguinofemoral/pelvic lymph node recurrence if prior external beam radiation therapy (EBRT); or for clinical nodal or distant recurrence with multiple pelvic nodes, distant metastasis, or prior pelvic EBRT when bevacizumab or a bevacizumab biosimilar in combination with cisplatin and paclitaxel or carboplatin and paclitaxel was not used previously

If the drug use is not on the FDA label, does not appear in the NCCN Guidelines or Triple-S has not published a Medical Policy covering the off-label use, then the drug use is not approved and the use of the drug is considered investigational.

Policy Guidelines

Table 1. Genomic Aberration Targeted Therapies (not all inclusive)

Sensitizing EGFR mutation-positive tumors	Afatinib − Erlotinib − Dacomitinib − Gefitinib − Osimertinib
ALK rearrangement-positive tumors	Alectinib − Brigatinib − Ceritinib − Crizotinib − Lorlatinib
ROS1 rearrangement-positive tumors	Ceritinib − Crizotinib − Entrectinib
BRAF V600E-mutation positive tumors	Dabrafenib ± Trametinib − Vemurafenib
NTRK Gene Fusion positive tumors	Larotrectinib − Entrectinib
PD-1/PD-L1 expression-positive tumors (>50%)	Pembrolizumab − Atezolizumab − Nivolumab ± ipilimumab
MET Exon-14 skipping mutations	Capmatinib − Crizotinib
RET rearrangement-positive tumors	Selpercatinib − Cabozantinib − Vandetanib

Coding:

See codes table.

Benefit Application

Requires authorization.

Triple-S Preferred Drugs Determinationsas

Triple-S Salud will consider the following agents as preferred: Zirabev & Mvasi for shared FDA approved conditions.

Non-Preferred Agents Step Therapy Criteria
Other Non Preferred Agents may be covered when the criteria listed under Sections A or B.
are satisfied:

A. Trial and failure of all of the following: Zirabev & Mvasi, resulting in minimal
clinical response to therapy
OR

B. History of intolerance or adverse event to all of the following: Zirabev & Mvasi.

FDA- Approved Indication	Avastin	Zirabev	Mvasi
Metastatic colorectal cancer, in combination with intravenous fluorouracil based chemotherapy for first- or second-line treatment	X	X	X
Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen	X	X	X
Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment.	X	X	X
Recurrent glioblastoma in adults.	X	X	X
Metastatic renal cell carcinoma in combination with interferon alfa.	X	X	X
Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan.	X	X	X
Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, for stage III or IV disease following initial surgical resection	X	X
Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens	X	X
Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by Avastin as a single agent, for platinum sensitive recurrent disease	X	X
Hepatocellular Carcinoma (HCC) in combination with atezolizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy	X

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

N/A

Regulatory Status

AVASTIN (bevacizumab) injection, for intravenous use FDA Initial U.S. Approval: 2004.

MVASI™ (bevacizumab-awwb) injection, for intravenous use Initial U.S. Approval: 2017

ZIRABEVTM (bevacizumab-bvzr) injection, for intravenous use Initial U.S. Approval: 2019

ALYMSYS® (bevacizumab-maly) injection, for intravenous use Initial U.S. Approval: 2022

VEGZELMA (bevacizumab-adcd) injection, for intravenous use Initial U.S. Approval: 2022

Criteria in this policy include FDA approved indications and NCCN Compendia off-label recommendations.

Rationale

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1

For individuals with colorectal cancer (CRC). Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 1

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 2

For individuals non-squamous non-small cell lung cancer (NSCLC). Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 2

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 3

For individuals with cervical cancer. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 3

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 4

For individuals with renal cell carcinoma (RCC). Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 4

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 5

For individuals with central nervous system (CNS) cancer. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 5

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 6

For individuals with ovarian cancer. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 6

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 7

For individuals with soft tissue sarcoma. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 7

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 8

For individuals with endometrial carcinoma. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 8

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 9

For individuals with malignant pleural mesothelioma. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 9

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 10

For individuals with vulvar cancer. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 10

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 11

For individuals with small bowel adenocarcinoma. Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 11

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Population Reference No. 12

For individuals with hepatocellular carcinoma (HCC). Interventions of interest is treatment with bevacizumab. Comparators of interest are oncologic treatment w/o bevacizumab. Relevant outcomes include: prevent tumor growth, prevent metastasis, improve life expectancy, improve the net health outcome. The evidence is sufficient to determine meaningful improvement in the net health outcome.

Population

Reference No. 12

Policy Statement

[X] MedicallyNecessary

[ ] Investigational

Avastin [package insert]. South San Francisco, CA; Genentech; June 2019.
Mvasi [package insert]. Thousand Oaks, CA; Amgen, Inc.; June 2019.
Zirabev [package insert]. New York, NY; Pfizer, Inc.; January 2020.
Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) bevacizumab. National Comprehensive Cancer Network, 2020. The NCCN. Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed November 2020.
Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for Anti-Cancer Chemotherapy for Colorectal Cancer (110.17) Accessed November 2020
Celltrion, Inc. Vegzelma (bevacizumab-adcd) injection, for intravenous use. Prescribing Information. Incheon, Republic of Korea: Celltrion; revised September 2022
Amneal Pharmaceuticals LLC. Alymsys (bevacizumab-maly) injection, for intravenous use. Prescribing Information. Bridgewater, NJ: Amneal Pharmaceuticals; revised April 2022

Codes

Codes	Number	Description
HCPCS	J9035	Injection Bevacizumab 10 MG
	Q5107	Injection, bevacizumab-awwb, biosimilar, (Mvasi), 10 mg
	Q5118	Injection, bevacizumab-bvcr, biosimilar, (Zirabev), 10 mg
	Q5126	Injection, bevacizumab-maly, biosimilar, (Alymsys), 10 mg
	Q5129	Injection, bevacizumab-adcd (Vegzelma), biosimilar, 10 mg
ICD-10-CM	C17.0	Malignant neoplasm duodenum
	C17.1	Malignant neoplasm jejunum
	C17.2	Malignant neoplasm ileum
	C17.8	Malignant neoplasm of overlapping sites of small intestines
	C17.9	Malignant neoplasm of small intestine, unspecified
	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 large intestines
	C18.9	Malignant neoplasm of colon, unspecified
	C19	Malignant neoplasm of rectosigmoid junction
	C20	Malignant neoplasm of rectum
	C21.8	Malignant neoplasm of overlapping sites of rectum, anus and anal canal
	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
	C24.1	Malignant neoplasm of ampulla of Vater
	C33	Malignant neoplasm of trachea
	C34.00	Malignant neoplasm of unspecified 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
	C34.2	Malignant neoplasm of middle lobe, bronchus or lung
	C34.30	Malignant neoplasm of lower lobe, unspecified bronchus or lung
	C34.31	Malignant neoplasm of lower lobe, right bronchus or lung
	C34.32	Malignant neoplasm of lower lobe, left bronchus or lung
	C34.80	Malignant neoplasm of overlapping sites of unspecified bronchus or lung
	C34.81	Malignant neoplasm of overlapping sites of right bronchus and lung
	C34.82	Malignant neoplasm of overlapping sites of left bronchus and lung
	C34.90	Malignant neoplasm of unspecified part of unspecified bronchus or lung
	C34.91	Malignant neoplasm of unspecified part of right bronchus or lung
	C34.92	Malignant neoplasm of unspecified part of left bronchus or lung
	C38.4	Malignant neoplasm of pleura
	C45.0	Mesothelioma of pleura
	C45.1	Mesothelioma of peritoneum
	C45.2	Mesothelioma of pericardium
	C45.7	Mesothelioma of other sites
	C45.9	Mesothelioma, unspecified
	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	Malignant neoplasm of connective and soft tissue of head, face and neck
	C49.10	Malignant neoplasm of connective and soft tissue of unspecified upper limb, including shoulder
	C49.11	Malignant neoplasm of connective and soft tissue of right upper limb including shoulder
	C49.12	Malignant neoplasm of connective and soft tissue of left upper limb, including shoulder
	C49.20	Malignant neoplasm of connective and soft tissue of unspecified lower limb, including hip
	C49.21	Malignant neoplasm of connective and soft tissue of right lower limb, including hip
	C49.22	Malignant neoplasm of connective and soft tissue of left lower limb, including hip
	C49.3	Malignant neoplasm of connective and soft tissue of thorax
	C49.4	Malignant neoplasm of connective and soft tissue of abdomen
	C49.5	Malignant neoplasm of connective and soft tissue of pelvis
	C49.6	Malignant neoplasm of connective and soft tissue of trunk, unspecified
	C49.8	Malignant neoplasm of overlapping sites of connective and soft tissue
	C49.9	Malignant neoplasm of connective and soft tissue, unspecified
	C51.0	Malignant neoplasm of labium majus
	C51.1	Malignant neoplasm of labium minus
	C51.2	Malignant neoplasm of clitoris
	C51.8	Malignant neoplasm of overlapping sites of vulva
	C51.9	Malignant neoplasm of vulva, unspecified
	C52	Malignant neoplasm of vagina
	C53.0	Malignant neoplasm of endocervix
	C53.1	Malignant neoplasm of exocervix
	C53.8	Malignant neoplasm of overlapping sites of cervix uteri
	C53.9	Malignant neoplasm of cervix uteri, unspecified
	C54.0	Malignant neoplasm of isthmus uteri
	C54.1	Malignant neoplasm of endometrium
	C54.2	Malignant neoplasm of myometrium
	C54.3	Malignant neoplasm of fundus uteri
	C54.8	Malignant neoplasm of overlapping sites of corpus uteri
	C54.9	Malignant neoplasm of corpus uteri, unspecified
	C55	Malignant neoplasm of uterus, part unspecified
	C56.1	Malignant neoplasm of right ovary
	C56.2	Malignant neoplasm of left ovary
	C56.9	Malignant neoplasm of unspecified ovary
	C57.00	Malignant neoplasm of unspecified fallopian tube
	C57.01	Malignant neoplasm of right fallopian tube
	C57.02	Malignant neoplasm of left fallopian tube
	C57.10	Malignant neoplasm of unspecified broad ligament
	C57.11	Malignant neoplasm of right broad ligament
	C57.12	Malignant neoplasm of left broad ligament
	C57.20	Malignant neoplasm of unspecified round ligament
	C57.21	Malignant neoplasm of right round ligament
	C57.22	Malignant neoplasm of left round ligament
	C57.3	Malignant neoplasm of parametrium
	C57.4	Malignant neoplasm of uterine adnexa, unspecified
	C57.7	Malignant neoplasm of other specified female genital organs
	C57.8	Malignant neoplasm of overlapping sites of female genital organs
	C57.9	Malignant neoplasm of female genital organ, unspecified
	C64.1	Malignant neoplasm of right kidney, except renal pelvis
	C64.2	Malignant neoplasm of left kidney, except renal pelvis
	C64.9	Malignant neoplasm of unspecified kidney, except renal pelvis
	C65.1	Malignant neoplasm of right renal pelvis
	C65.2	Malignant neoplasm of left renal pelvis
	C65.9	Malignant neoplasm of unspecified renal pelvis
	C70.0	Malignant neoplasm of cerebral meninges
	C70.1	Malignant neoplasm of spinal meninges
	C70.9	Malignant neoplasm of meninges, unspecified
	C71.0	Malignant neoplasm of cerebrum, except lobes and ventricles
	C71.1	Malignant neoplasm of frontal lobe
	C71.2	Malignant neoplasm of temporal lobe
	C71.3	Malignant neoplasm of parietal lobe
	C71.4	Malignant neoplasm of occipital lobe
	C71.5	Malignant neoplasm of cerebral ventricle
	C71.6	Malignant neoplasm of cerebellum
	C71.7	Malignant neoplasm of brain stem
	C71.8	Malignant neoplasm of overlapping sites of brain
	C71.9	Malignant neoplasm of brain, unspecified
	C72.0	Malignant neoplasm of spinal cord
	C72.1	Malignant neoplasm of cauda equina
	C72.9	Malignant neoplasm of central nervous system, unspecified
	C78.00	Secondary malignant neoplasm of unspecified lung
	C78.01	Secondary malignant neoplasm of right lung
	C78.02	Secondary malignant neoplasm of left lung
	C78.6	Secondary malignant neoplasm of retroperitoneum and peritoneum
	C78.7	Secondary malignant neoplasm of liver and intrahepatic bile duct
	C79.00	Secondary malignant neoplasm of unspecified kidney and renal pelvis
	C79.01	Secondary malignant neoplasm of right kidney and renal pelvis
	C79.02	Secondary malignant neoplasm of left kidney and renal pelvis
	C79.19	Secondary malignant neoplasm of other urinary organs
	C79.31	Secondary malignant neoplasm of brain
	C79.32	Secondary malignant neoplasm of cerebral meninges
	C79.82	Secondary malignant neoplasm of genital organs
	C83.30	Diffuse large B-cell lymphoma unspecified site
	C83.31	Diffuse large B-cell lymphoma lymph nodes of head, face, and neck
	C83.39	Diffuse large B-cell lymphoma extranodal and solid organ sites
	C83.390	Primary central nervous system lymphoma
	C83.398	Diffuse large B-cell lymphoma of other extranodal and solid organ sites
	C83.59	Lymphoblastic (diffuse) lymphoma, extranodal and solid organ sites
	C83.79	Burkitt lymphoma, extranodal and solid organ sites
	C83.80	Other non-follicular lymphoma unspecified site
	C83.81	Other non-follicular lymphoma lymph nodes of head, face, and neck
	C83.89	Other non-follicular lymphoma extranodal and solid organ sites
	C84.49	Peripheral T-cell lymphoma, not elsewhere classified, extranodal and solid organ sites
	C85.89	Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites
	C85.99	Non-Hodgkin lymphoma, unspecified, extranodal and solid organ sites
	D32.0	Benign neoplasm of cerebral meninges
	D32.1	Benign neoplasm of spinal meninges
	D32.9	Benign neoplasm of meninges, unspecified
	D42.0	Neoplasm of uncertain behavior of cerebral meninges
	D42.1	Neoplasm of uncertain behavior of spinal meninges
	D42.9	Neoplasm of uncertain behavior of meninges, unspecified
	D43.0	Neoplasm of uncertain behavior of brain, supratentorial
	D43.1	Neoplasm of uncertain behavior of brain, infratentorial
	D43.2	Neoplasm of uncertain behavior of brain, unspecified
	D43.4	Neoplasm of uncertain behavior of spinal cord
	D43.9	Neoplasm of uncertain behavior of central nervous system, unspecified
	Q85.02	Neurofibromatosis, type 2
	Q85.03	Schwannomatosis
	Q85.83	Von Hippel-Lindau syndrome
	Z85.038	Personal history of other malignant neoplasm of large intestine
	Z85.068	Personal history of other malignant neoplasm of small intestine
	Z85.09	Personal history of malignant neoplasm of other digestive organs
	Z85.118	Personal history of other malignant neoplasm of bronchus and lung
	Z85.42	Personal history of malignant neoplasm of other parts of uterus
	Z85.43	Personal history of malignant neoplasm of ovary
	Z85.528	Personal history of other malignant neoplasm of kidney
	Z85.831	Personal history of malignant neoplasm of soft tissue
	Z85.841	Personal history of malignant neoplasm of brain
	Z85.848	Personal history of malignant neoplasm of other parts of nervous tissue

Policy History

Date	Action	Description
10/24/2024	Annual Review	ICD-10-CM Diagnosis codes reviewed (Added: C22.0 C22.8 C22.9 C24.1 C45.1 C45.2 C45.7 C45.9 C52 C72.1 C83.390 C83.398 C83.59 C83.79 C84.49 C85.99 D43.9 Q85.02 Q85.03 Q85.83 Z85.09 Z85.42). No changes to policy statement. Approved by the Providers Advisory Committee
10/26/2023	Annual Review	Added biosimilars bevacizumab-maly, biosimilar, (Alymsys) HCPCS Q5126, bevacizumab-adcd (Vegzelma) HCPCS Q5129. Breast cancer indication removed, References updated.
8/28/2023	Policy Review	Update policy with deletion of reference to naive patients in Benefit Application section. Deletion of section C that make reference to continuation of therapy within the last 365 days.
11/09/2022	Annual Review	Reviwed by the Providers Advisory Board. Added FDA indication for Cervical cancer - in combination with pembrolizumab and chemotherapy for persistent, metastatic, or recurrent disease with a PD-L1 combined positive score ≥ 1%. Added Off Label indications for Ampullary Adenocarcinoma and Appendiceal Adenocarcinoma.
11/10/2021	Annual Review	Policy statement format changed and updated. Revision with latest guidelines by recommendation of the Provider Advisory Committee.
11/11/2020	Annual Review	Avastin biosimilars added. Revision with latest guidelines by recommendation of the Provider Advisory Committee. PICOs, Policy statement and codes updated due to latest NCCN recommendations. Biosimilars preferred status added.
11/14/2019	Annual Review	Presented at Provider Advisory Committee. No changes.
06/01/2019	Out of Schedule Revision	New Policy Format, diagnosis code added
11/13/2017
09/16/2016
10/16/2015
12/29/2014
08/20/2014	ICD-10 Added
08/18/2014
10/16/2013
04/03/2013

Bevacizumab

Summary

Objective

Policy Statements

Policy Guidelines

Benefit Application

Background

Regulatory Status

Rationale

Supplemental Information

Practice Guidelines and Position Statements

Medicare National Coverage

References

Codes

Policy History