vp-0096
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Perjeta® (pertuzumab) (Intravenous)

Policy Number: VP-0096

Last Review Date: 12/01/2020

Date of Origin: 11/01/2012

Dates Reviewed: 12/2012, 03/2013, 06/2013, 09/2013, 11/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 6/2020, 09/2020, 12/2020

I. Length of Authorization 

Coverage is provided for 6 months and may be renewed (unless otherwise specified).

  • Use for neo-adjuvant and adjuvant breast cancer is limited to a total of 1 year of treatment [18 cycles] (*Note: When used for metastatic breast cancer, therapy may be continued until disease progression or unmanageable toxicity.)

II. Dosing Limits

  1. Quantity Limit (max daily dose) [NDC Unit]:

Perjeta 420 mg/14mL solution for injection:

  • Loading Dose: 2 vials
  • Maintenance Doses: 1 vial every 21 days
  1. Max Units (per dose and over time) [HCPCS Unit]:

Loading Dose

  • 840 billable units x 1 dose

Maintenance Dose

  • 420 billable units every 21 days

III. Initial Approval Criteria 

Coverage is provided in the following conditions:

  • Patient is at least 18 years of age; AND

Universal Criteria 

  • Left ventricular ejection fraction (LVEF) is within normal limits prior to initiating therapy and will be assessed at regular intervals (e.g., every 3 months) during treatment; AND
  • Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
  • Therapy will not be used in combination with pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo); AND

Breast Cancer † 

  • Used as adjuvant treatment; AND
    • Patient has locally advanced or node positive disease OR early stage disease at high risk of recurrence; AND
    • Used in combination with a trastuzumab-based regimen; OR
  • Used as neoadjuvant treatment for breast preservation; AND
    • Patient has locally advanced, inflammatory, or early stage disease; AND
    • Used in combination with trastuzumab and chemotherapy; OR
  • Used for recurrent or metastatic disease; AND
          •  
    • Used as first-line therapy in combination with trastuzumab and either paclitaxel OR docetaxel; OR
    • Used as second-line therapy in combination with a trastuzumab-based regimen ; AND
          •  
      • Patient was previously treated with trastuzumab and chemotherapy; AND
      • Patient has not previously received pertuzumab

Colorectal Cancer ‡ 

  • Used for RAS and BRAF wild-type (WT) disease in combination with trastuzumab in patients who have not previously received HER2-targeted therapy; AND
    • Used as subsequent therapy for progression of advanced or metastatic disease after at least one prior line of treatment in the advanced or metastatic disease setting; OR
    • Patient is not appropriate for intensive therapy; AND
      • Used as initial systemic therapy for locally unresectable (or medically inoperable) or metastatic disease; OR
      • Used for unresectable or metastatic disease that remains unresectable after primary treatment; OR
      • Used for metastatic disease in patients who have received adjuvant FOLFOX or CapeOX more than 12 months ago OR who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy

*HER2-positive overexpression criteria:

  • Immunohistochemistry (IHC) assay 3+; OR
  • Dual-probe in situ hybridization (ISH) assay HER2/CEP17 ratio2.0 AND average HER2 copy number 4.0 signals/cell; OR
  • Dual-probe in situ hybridization (ISH) assay AND concurrent IHC indicating one of the following:
          • HER2/CEP17 ratio 2.0 AND average HER2 copy number < 4.0 signals/cell AND concurrent IHC 3+; OR
          • HER2/CEP17 ratio < 2.0 AND average HER2 copy number 6.0 signals/cell AND concurrent IHC 2+ or 3+; OR
          • HER2/CEP17 ratio < 2.0 AND average HER2 copy number ≥ 4.0 and < 6.0 signals/cell AND concurrent IHC 3+

v If confirmed using an immunotherapy assay-http://www.fda.gov/companiondiagnostics

FDA Approved Indication(s); Compendia recommended indication(s); Ф Orphan Drug

IV. Renewal Criteria 

Coverage can be renewed based upon the following criteria:

  • Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
  • Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
  • Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: left ventricular dysfunction, severe infusion-related reactions, hypersensitivity reactions/anaphylaxis, etc.; AND
  • Left ventricular ejection fraction (LVEF) is >45% OR LVEF is ≥40% and absolute decrease is <10% from baseline (LVEF results must be within the previous 3 months); AND
  • Use for neoadjuvant and adjuvant breast cancer treatment is limited to a total of 1 year of treatment (total of 18 cycles)

V. Dosage/Administration 

Indication

Dose

Breast Cancer

Administer 840 mg intravenously x 1 dose, then 420 mg intravenously every 21 days thereafter until disease progression or unmanageable toxicity

  • Neoadjuvant therapy consists of 3 to 6 cycles prior to surgery
  • Use for neoadjuvant and adjuvant early breast cancer treatment is limited to a total of 1 year of treatment (total of 18 cycles)

*Note: When used for metastatic breast cancer, therapy may be continued until disease progression or unmanageable toxicity.

Colorectal Cancer

Administer 840 mg intravenously x 1 dose, then 420 mg intravenously every 21 days thereafter until disease progression or unmanageable toxicity

VI. Billing Code/Availability Information

HCPCS Code:

  • J9306 - Injection, pertuzumab, 1 mg; 1 mg = 1 billable unit

NDC:

  • Perjeta 420 mg/14 mL single-dose vial for injection: 50242-0145-xx

VII. References

  1. Perjeta [package insert]. South San Francisco, CA; Genentech, Inc.; January 2020. Accessed October 2020.
  2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) pertuzumab. 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 October 2020.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer 6.2020. National Comprehensive Cancer Network, 2020. 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 Guidelines, go online to NCCN.org. Accessed October 2020.
  4. Wolff AC, Hammond EH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 2018;36:2105-2122.
  5. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32.
  6. Baselga J, Cortes J, Kim SB, et al. CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109-119.
  7. Schneeweiss A., Chia S., Hickish T., et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24 (9): 2278-2284.
  8. von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017;377(2):122-131.
  9. Hainsworth JD, Meric-Bernstam F, Swanton C, et al. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. Clin Oncol. 2018 Feb 20;36(6):536-542.
  10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer 4.2020. National Comprehensive Cancer Network, 2020. 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 Guidelines, go online to NCCN.org. Accessed October 2020.
  11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer 6.2020. National Comprehensive Cancer Network, 2020. 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 Guidelines, go online to NCCN.org. Accessed October 2020.
  12. Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019;20(4):518-530. doi:10.1016/S1470-2045(18)30904-5.
  13. Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29(3):646-653. doi:10.1093/annonc/mdx773.
  14. Palmetto GBA, LLC. Local Coverage Article: Billing and Coding: Chemotherapy (A56141). Centers for Medicare and Medicaid Services, Inc. Updated on 05/26/2020 with effective date 04/30/2020. Accessed October 2020.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

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

C50.011

Malignant neoplasm of nipple and areola, right female breast

C50.012

Malignant neoplasm of nipple and areola, left female breast

C50.019

Malignant neoplasm of nipple and areola, unspecified female breast

C50.021

Malignant neoplasm of nipple and areola, right male breast

C50.022

Malignant neoplasm of nipple and areola, left male breast

C50.029

Malignant neoplasm of nipple and areola , unspecified male breast

C50.111

Malignant neoplasm of central portion of right female breast

C50.112

Malignant neoplasm of central portion of left female breast

C50.119

Malignant neoplasm of central portion of unspecified female breast

C50.121

Malignant neoplasm of central portion of right male breast

C50.122

Malignant neoplasm of central portion of left male breast

C50.129

Malignant neoplasm of central portion of unspecified male breast

C50.211

Malignant neoplasm of upper-inner quadrant of right female breast

C50.212

Malignant neoplasm of upper-inner quadrant of left female breast

C50.219

Malignant neoplasm of upper-inner quadrant of unspecified  female breast

C50.221

Malignant neoplasm of upper-inner quadrant of right male breast

C50.222

Malignant neoplasm of upper-inner quadrant of left male breast

C50.229

Malignant neoplasm of upper-inner quadrant of unspecified male breast

C50.311

Malignant neoplasm of lower-inner quadrant of right female breast

C50.312

Malignant neoplasm of lower-inner quadrant of left female breast

C50.319

Malignant neoplasm of lower-inner quadrant of unspecified female breast

C50.321

Malignant neoplasm of lower-inner quadrant of right male breast

C50.322

Malignant neoplasm of lower-inner quadrant of left male breast

C50.329

Malignant neoplasm of lower-inner quadrant of unspecified male breast

C50.411

Malignant neoplasm of upper-outer quadrant of right female breast

C50.412

Malignant neoplasm of upper-outer quadrant of left female breast

C50.419

Malignant neoplasm of upper-outer quadrant of unspecified female breast

C50.421

Malignant neoplasm of upper-outer quadrant of right male breast

C50.422

Malignant neoplasm of upper-outer quadrant of left male breast

C50.429

Malignant neoplasm of upper-outer quadrant of unspecified male breast

C50.511

Malignant neoplasm of lower-outer quadrant of right female breast

C50.512

Malignant neoplasm of lower-outer quadrant of left female breast

C50.519

Malignant neoplasm of lower-outer quadrant of unspecified female breast

C50.521

Malignant neoplasm of lower-outer quadrant of right male breast

C50.522

Malignant neoplasm of lower-outer quadrant of left male breast

C50.529

Malignant neoplasm of lower-outer quadrant of unspecified male breast

C50.611

Malignant neoplasm of axillary tail of right female breast

C50.612

Malignant neoplasm of axillary tail of left female breast

C50.619

Malignant neoplasm of axillary tail of unspecified female breast

C50.621

Malignant neoplasm of axillary tail of right male breast

C50.622

Malignant neoplasm of axillary tail of left male breast

C50.629

Malignant neoplasm of axillary tail of unspecified male breast

C50.811

Malignant neoplasm of overlapping sites of right female breast

C50.812

Malignant neoplasm of overlapping sites of left female breast

C50.819

Malignant neoplasm of overlapping sites of unspecified female breast

C50.821

Malignant neoplasm of overlapping sites of right male breast

C50.822

Malignant neoplasm of overlapping sites of left male breast

C50.829

Malignant neoplasm of overlapping sites of unspecified male breast

C50.911

Malignant neoplasm of unspecified site of right female breast

C50.912

Malignant neoplasm of unspecified site of left female breast

C50.919

Malignant neoplasm of unspecified site of unspecified female breast

C50.921

Malignant neoplasm of unspecified site of right male breast

C50.922

Malignant neoplasm of unspecified site of left male breast

C50.929

Malignant neoplasm of unspecified site of unspecified male breast

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

Z85.038

Personal history of other malignant neoplasm of large intestine

Z85.068

Personal history of other malignant neoplasm of small intestine

Z85.3

Personal history of malignant neoplasm of breast

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA):

.

Jurisdiction(s): J & M

NCD/LCD/LCA Document (s): A56141

https://www.cms.gov/medicare-coverage-database/search/lcd-date-search.aspx?DocID=A56141&bc=gAAAAAAAAAAA

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC