RXMP-02 Bevacizumab for Non-Ophthalmologic Indications Form

Page 1 of 7

AlohaCare Medical Policy Bevacizumab for Non-Ophthalmologic Indications

Policy Number:
RXMP-02 Effective Date:
9/4/2019 Review Date:
10/20/2025 Plans AlohaCare Medicaid & Medicare

PRODUCTS: Alymsys, Avastin, Mvasi, Vegzelma, Zirabev

HCPCS Code Description Drug Name J9035 Injection, bevacizumab, 10 mg Avastin 100mg/4mL inj (bevacizumab) Q5107 Injection, bevacizumab-awwb, biosimilar, (Mvasi), 10 mg (preferred) Mvasi 100mg/4mL inj (bevacizumab- awwb) (preferred) Q5118 Injection, bevacizumab-bvcr, biosimilar, (Zirabev), 10 mg (preferred) Zirabev 100mg/4mL inj (bevacizumab- bvzr) (preferred) Q5126 Injection, bevacizumab-maly, biosimilar, 10 mg Alymsys (bevacizumab-maly) Q5129 Injection, bevacizumab-adcd, biosimilar, 10 mg Vegzelma (bevacizumab-adcd) Medicare (New Starts)/Medicaid preferred agents: Mvasi or Zirabev

Formulary Status: Medical Benefit: Authorization Required
Pharmacy Benefit: Excluded to Medical Benefit Duration of Approval: Initial Request: 3 months COC/Reauthorization: 12 months Dosing Limit: See dosing information

MEDICARE CMS CRITERIA: • Review using the most current Local Coverage Determination (LCD), National Coverage Determination (NCD), or Local Coverage Article (LCA) that applies to the Hawaii region. The LCD, NCD, or LCA can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. • NCD as of 10/20/2025: NCD 110.17 Anti-Cancer Chemotherapy for Colorectal Cancer
• No LCD/NCD/LCA found for other uses as of 10/20/2023 (cancer Dx). • For new starts, step therapy criteria must be met in addition to clinical criteria before a request may be approved.

MEDICARE PART B STEP THERAPY CRITERIA: Avastin, Alymsys, and Vegzelma (new starts): The member has an inadequate response to, intolerable adverse event to, or has a contraindication to Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab- bvzr).

CONTINUATION CRITERIA FOR APPROVAL FOR MEDICARE/MEDICAID: ➢ Pharmacy staff: For QUEST & non-ABD members with cancer, send ADRC referral with chart notes. MEDICARE PART B 90-DAY TRANSITION PERIOD:
For new Medicare members, a 90-day transition period applies. During this time, if a member is currently on an active course of the requested treatment, including when furnished by an out-of- network provider, Coverage and Step Therapy do not apply. After the first 90 days of enrollment, Coverage and Step Therapy Criteria must be met for continued coverage.

Page 2 of 7 For All Indications – for Medicare use the NCD criteria above

1. Member does not show evidence of progressive disease while on therapy AND

2. For Medicaid: Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab- bvzr).

   INITIAL CRITERIA FOR APPROVAL FOR MEDICARE/MEDICAID: ➢ Pharmacy staff: For QUEST & non-ABD members with cancer, send ADRC referral with chart notes.

   Cervical Cancer

3. Diagnosis of carcinoma of the cervix AND
4. Disease is one of the following:
   a. Persistent
   b. Recurrent
   c. Metastatic
   AND
5. Used in combination with one of the following:
   d. Paclitaxel and cisplatin
   e. Paclitaxel and topotecan
   AND
6. Prescribed by or in consultation with an oncologist AND

7. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

   Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

8. One of the following diagnoses:
   a. Epithelial ovarian cancer
   b. Fallopian tube cancer
   c. Primary peritoneal cancer
   AND
9. One of the following (a, b, or c) a. All of the following (1-4) 1) Disease is stage 3 or 4
   2) Patient has been treated with bevacizumab as a single agent
   3) Treatment is following surgical resection
   4) Used in combination with both of the following:
   a) Carboplatin
   b) Paclitaxel
   OR b. All of the following:
   1) Disease is platinum-resistant recurrent AND Member has received no more than two prior chemotherapy regimens
   2) Used in combination with one of the following:
   a) Paclitaxel
   b) Pegylated liposomal doxorubicin
   c) Topotecan
   OR c. All of the following:
   1) Disease is platinum-sensitive recurrent
   2) Patient has been treated with bevacizumab as a single agent
   3) Used in combination with one of the following:

Page 3 of 7 a) Carboplatin and paclitaxel
b) Carboplatin and gemcitabine
AND

3. Prescribed by or in consultation with an oncologist AND

4. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

   Glioblastoma

5. Diagnosis of recurrent glioblastoma AND
6. Prescribed by or in consultation with an oncologist AND

7. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

   Hepatocellular Carcinoma

8. Diagnosis of hepatocellular carcinoma AND
9. Disease is one of the following:
   a. Unresectable
   b. Metastatic
   AND
10. Used in combination with Tecentriq (atezolizumab) AND
11. Member has not received prior systemic therapy AND
12. Prescribed by or in consultation with an oncologist AND

13. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

    Metastatic Colorectal Cancer – for Medicare use the NCD criteria above.

14. Diagnosis of metastatic colorectal cancer AND
15. One of the following (a or b): a. Used as first- or second-line treatment AND in combination with an intravenous 5-fluorouracil- based chemotherapy b. Used as second-line treatment AND in combination with one of the following (1 or 2):
    1) fluoropyrimidine-irinotecan-based chemotherapy [e.g., capecitabine, floxuridine, and fluorouracil (5-FU)]
    2) fluoropyrimidine-oxaliplatin-based chemotherapy [e.g., capecitabine, floxuridine, and fluorouracil (5-FU)]
    AND 3) Member has progressed on a first-line bevacizumab-containing regimen
    AND
16. Prescribed by or in consultation with an oncologist AND

17. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

    Non-Small Cell Lung Cancer (NSCLC)

18. Diagnosis of non-small cell lung cancer (NSCLC) AND
19. Disease is one of the following:
    a. Unresectable
    b. Locally advanced

Page 4 of 7 c. Recurrent
d. Metastatic
AND

3. Used as first-line treatment AND
4. Used in combination with both of the following:
   • Paclitaxel
   • Carboplatin
   AND
5. Member does not have squamous cell histology AND
6. The medication was prescribed by or in consultation with an oncologist AND

7. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

   Renal Cell Cancer

8. Diagnosis of metastatic renal cell cancer AND
9. Used in combination with interferon-alfa AND
10. Prescribed by or in consultation with an oncologist AND

11. For Medicaid: Request for Avastin, Alymsys, Vegzelma: The member has an inadequate response to, intolerable adverse event to, or has a contraindication for Mvasi (bevacizumab-awwb) or Zirabev (bevacizumab-bvzr).

    EXCLUSION:

    FDA INDICATIONS, DOSING & ADMINISTRATION: Drug Name Dosing/Administration Cervical cancer, Recurrent, persistent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan In combination with paclitaxel and either cisplatin or topotecan: 15 mg/kg intravenous (IV) infusion every 3 weeks. Continue until disease progression or unacceptable toxicity. Glioblastoma 10 mg/kg IV infusion every 2 weeks. Liver carcinoma, Unresectable or metastatic, in combination with atezolizumab, in those who have not received prior systemic therapy 15 mg/kg IV after administration of atezolizumab 1200 mg IV on the same day, every 3 weeks until disease progression or unacceptable toxicity Metastatic colorectal cancer, First-line therapy, in combination with oxaliplatin and capecitabine (First-line therapy with XELOX (oxaliplatin and capecitabine)) 7.5 mg/kg given IV over 30 to 90 minutes every 3 weeks. Give with XELOX: oxaliplatin 130 mg/m(2) IV over 2 hours day 1 followed by capecitabine 1000 mg/m(2) twice daily days 1 to 14 (off-label dosage) Metastatic colorectal cancer, First- or second-line therapy, in combination with IV 5- fluorouracil-based chemotherapy • (With IFL regimen) 5 mg/kg IV infusion every 2 weeks in combination with bolus-IFL until disease progression or unacceptable toxicity. Give with bolus-IFL: irinotecan 125 mg/m(2) IV, 5-fluorouracil 500 mg/m(2) IV, and leucovorin 20 mg/m(2) IV once weekly for 4 weeks every 6 weeks; continue until disease progression or intolerable toxicity (FDA dosage). • (With FOLFOX-4 regimen) 10 mg/kg IV infusion every 2 weeks in combination with FOLFOX4 until disease progression or unacceptable toxicity. Give with FOLFOX4: Day 1, oxaliplatin 85 mg/m(2) IV and leucovorin 200 mg/m(2) IV given concurrently, followed by 5- fluorouracil 400 mg/m(2) IV bolus then 5-fluorouracil 600 mg/m(2) IV

Page 5 of 7 Drug Name Dosing/Administration continuously; Day 2, leucovorin 200 mg/m(2) IV followed by 5- fluorouracil 400 mg/m(2) IV bolus then 5-fluorouracil 600 mg/m(2) IV continuously; continue until disease progression or intolerable toxicity (FDA dosage) • (With FOLFOXIRI regimen) 5 mg/kg IV plus irinotecan 165 mg/m(2) over 60 minutes, then oxaliplatin 85 mg/m(2) concurrently with leucovorin 200 mg/m(2) over 120 minutes, followed by fluorouracil 3200 mg/m(2) continuous IV infusion for 48 hours; repeat cycles every 14 days for up to 12 cycles (off-label dosage)
• (With FOLFIRI regimen): 5 mg/kg IV plus irinotecan 180 mg/m(2) IV, then leucovorin 200 mg/m(2) IV over 120 minutes, then fluorouracil 400 mg/m(2) IV bolus and 2400 mg/m(2) continuous infusion for 46 hours; repeat cycles every 14 days for up to 12 cycles (off-label dosage) Metastatic colorectal cancer, in previously untreated elderly patients, ineligible for oxaliplatin- or irinotecan- based chemotherapy 7.5 mg/kg IV once every 3 weeks until disease progression. Give with capecitabine 1000 mg/m(2) orally twice daily on days 1 to 14 (off-label dosage) Metastatic colorectal cancer, second-line therapy, in combination with fluoropyrimidine/irinotecan- or fluoropyrimidine/ oxaliplatin-based chemotherapy, in patients who have progressed on a first-line bevacizumab product-containing regimen 7.5 mg/kg IV once every 3 weeks until disease progression. Give with capecitabine 1000 mg/m(2) orally twice daily on days 1 to 14 (off-label dosage) Metastatic renal cell carcinoma, in combination with interferon alfa 10 mg/kg IV infusion every 2 weeks in combination with interferon alfa until disease progression or unacceptable toxicity. Give with interferon alfa-2a 9 million international units subQ 3 times per week for a maximum of 52 weeks Nonsquamous non-small cell lung cancer, recurrent or metastatic, unresectable, locally advanced, first-line treatment in combination with paclitaxel and carboplatin 15 mg/kg IV infusion every 3 weeks in combination with paclitaxel and carboplatin until disease progression or unacceptable toxicity. Give with paclitaxel 200 mg/m(2) IV and carboplatin IV AUC 6 on day 1 of every 21-day cycle
Ovarian cancer, Fallopian tube or primary peritoneal cancer, recurrent, platinum-resistant disease, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, with no more than 2 prior chemotherapy regimens • 10 mg/kg IV infusion every 2 weeks in combination with IV paclitaxel, pegylated liposomal doxorubicin, or topotecan until disease progression or unacceptable toxicity. Give with paclitaxel 80 mg/m(2) IV on days 1, 8, 15, and 22 every 4 weeks; or pegylated liposomal doxorubicin 40 mg/m(2) IV on day 1 every 4 weeks; or topotecan 4 mg/m(2) IV on days 1, 8, and 15 every 4 weeks • 15 mg/kg IV infusion every 3 weeks in combination with topotecan 1.25 mg/m(2) IV on days 1 to 5 every 3 weeks until disease progression or unacceptable toxicity. If tolerated, the bevacizumab infusion may be given over 60 minutes for the second infusion and over 30 minutes for subsequent infusions
Ovarian cancer, Fallopian tube or primary peritoneal cancer, • 15 mg/kg IV infusion every 3 weeks in combination with IV carboplatin and paclitaxel for 6 to 8 cycles, followed by single-agent bevacizumab

Page 6 of 7 Drug Name Dosing/Administration recurrent, platinum-sensitive disease, in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by single agent bevacizumab 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity. Give with paclitaxel 175 mg/m(2) IV over 3 hours and carboplatin AUC 5 on day 1 of 21-day cycles for 6 cycles; up to 8 cycles allowed • 15 mg/kg IV infusion every 3 weeks in combination with IV carboplatin and gemcitabine for 6 to 10 cycles, followed by single-agent bevacizumab 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity. Give with gemcitabine 1000 mg/m(2) on days 1 and 8 and carboplatin AUC 4 on day 1 of 21-day cycles for 6 cycles; up to 10 cycles allowed
Ovarian cancer, Stage III or IV epithelial ovarian, fallopian tube or primary peritoneal cancer, first-line therapy in combination with carboplatin and paclitaxel following initial surgical resection, followed by single-agent bevacizumab 15 mg/kg IV every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 weeks alone for up to 22 cycles or until disease progression

Diagnosis Avastin (bevacizumab) Alymsys (bevacizumab- maly) Mvasi (bevacizumab- awwb) Vegzelma (bevacizumab- adcd) Zirabev (bevacizumab- bvzr) Central Nervous System Cancer Y Y Y Y Y Cervical Cancer X X X X X Colorectal Cancer X X X X X Ovarian, Fallopian Tube, or Primary Peritoneal Cancer X X Y X X Hepatobiliary Carcinoma X Y Y Y Y Malignant Mesothelioma Y Y Y Y Y Non-small cell lung cancer X X X X X Recurrent Glioblastoma X X X X X Renal Cell Carcinoma X X X X X Small Bowel Adenoocarcinoma Y Y Y Y Y Soft Tissue Sarcoma Y Y Y Y Y Vulvar Cancer Y Y Y Y Y X = FDA approved used; Y = Off-label indication

REFERENCES:

1. OptumRx, PA criteria, accessed May 2023.
2. CodeSource, accessed May 2023.
3. Micromedix, accessed May 2023.

Page 7 of 7 Change History:

1. bevacizumab (Avastin), retired May 2023, HB.
2. Bevacizumab for Non-Ophthalmologic Indications, new as of 5/23/2023, HB.
3. Added Continuity of Care requirement 4/2/2025, AP. 4.