vp-0522
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Enhertu® (fam-trastuzumab deruxtecan-nxki) (Intravenous)

Policy Number: VP-0522

Last Review Date: 02/02/2021

Date of Origin: 02/04/2020

Dates Reviewed: 02/2020, 06/2020, 09/2020, 02/2021

FOR PEEHIP Members Only -Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

I. Length of Authorization

Coverage will be provided for six months and may be renewed.

II. Dosing Limits

  1. Quantity Limit (max daily dose) [NDC Unit]:
  • Enhertu 100 mg vial: 7 vials every 21 days 
  1. Max Units (per dose and over time) [HCPCS Unit]:
  • Breast Cancer: 600 billable units every 21 days
  • All other indications: 700 billable units every 21 days

III. Initial Approval Criteria 

Coverage is provided in the following conditions:

  • Patient 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; AND
  • Used as single agent therapy; AND
  • Therapy will not be substituted with or for any trastuzumab-based formulation (i.e., trastuzumab [or trastuzumab biosimilar product], ado-trastuzumab emtansine, trastuzumab-hyaluronidase, pertuzumab/trastuzumab and hyaluronidase-zzxf, etc.); AND

Breast Cancer † ‡ 

  • Patient has recurrent, unresectable, or metastatic disease; AND
  • Patient has previously been treated with at least two (2) prior HER2-targeted therapies for metastatic disease

Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma † 

  • Patient has locally advanced or metastatic disease; AND
  • Patient has previously been treated with a trastuzumab-based regimen

Colorectal Adenocarcinoma ‡ 

  • Patient has RAS and BRAF wild-type (WT) disease; 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

Non-Small Cell Lung Cancer (NSCLC) ‡ 

  • Patient has metastatic disease

† FDA approved indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

*HER2-positive overexpression criteria: 
  • Immunohistochemistry (IHC) assay 3+; OR
  • Dual-probe in situ hybridization (ISH) assay HER2/CEP17 ratio ≥ 2.0 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+

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 the following: left ventricular dysfunction/symptomatic congestive heart failure, pulmonary toxicity (i.e., interstitial lung disease/pneumonitis), neutropenia/febrile neutropenia, etc.; AND
    • LVEF is > 45% and absolute decrease is ≤ 20% from baseline (LVEF results must be within the previous 3 months); OR
    • LVEF is 40% to 45% and absolute decrease is < 10% from baseline (LVEF results must be within the previous 3 months)

V. Dosage/Administration 

Indication

Dose

Breast Cancer

Administer 5.4 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity

Gastric/Gastroesophageal Junction (GEJ) Adenocarcinoma

Administer 6.4 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity

Colorectal Adenocarcinoma

Administer 6.4 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity

Non-Small Cell Lung Cancer

Administer 6.4 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity

VI. Billing Code/Availability Information

HCPCS Code:

  • J9358 – Injection, fam-trastuzumab deruxtecan-nxki, 1 mg: 1 billable unit = 1 mg

NDC:

  • Enhertu 100 mg single-dose vial: 65597-0406-xx 

VII. References

  1. Enhertu [package insert]. Basking Ridge, NJ; Daiichi Sankyo, Inc; January 2021. Accessed January 2021.
  2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) fam-trastuzumab deruxtecan. National Comprehensive Cancer Network, 2021. 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 January 2021.
  3. Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer 1.2021. National Comprehensive Cancer Network, 2021. 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 January 2021.
  2. 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.
  3. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf
  4. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
  5. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2019 Dec 11. Doi: 10.1056/NEJMoa1914510.
  6. Shitara K, Bang YJ, Iwasa S, et al; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430.
  7. Siena S, Di Bartolomeo M, Raghav KPS, et al. A phase II, multicenter, open-label study of trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol 2020;38(suppl; abstr 4000).
  8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer 1.2021. National Comprehensive Cancer Network, 2021. 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 January 2021.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer 1.2021. National Comprehensive Cancer Network, 2021. 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 January 2021.
  10. Smit EF, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): interim results of DESTINY-Lung01[abstract]. J Clin Oncol 2020;38:Abstract 9504.
  11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer 2.2021. National Comprehensive Cancer Network, 2021. 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 January 2021.
  12. First Coast Service Options, Inc. Local Coverage Article: Billing and Coding: Trastuzumab -Trastuzumab Biologics (A56660). Centers for Medicare & Medicaid Services, Inc. Updated on 7/22/2020 with effective date of 7/1/2020. Accessed January 2021.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

C15.3

Malignant neoplasm of upper third of esophagus

C15.4

Malignant neoplasm of middle third of esophagus

C15.5

Malignant neoplasm of the lower third of esophagus

C15.8

Malignant neoplasm of overlapping sites of esophagus

C15.9

Malignant neoplasm of esophagus, unspecified

C16.0

Malignant neoplasm of cardia

C16.1

Malignant neoplasm of fundus of stomach

C16.2

Malignant neoplasm of body of stomach

C16.3

Malignant neoplasm of pyloric antrum

C16.4

Malignant neoplasm of pylorus

C16.5

Malignant neoplasm of lesser curvature of stomach, unspecified

C16.6

Malignant neoplasm of greater curvature of stomach, unspecified

C16.8

Malignant neoplasm of overlapping sites of stomach

C16.9

Malignant neoplasm of stomach, unspecified

C17.0

Malignant neoplasm of duodenum

C17.1

Malignant neoplasm of jejunum

C17.2

Malignant neoplasm of ileum

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0

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 colon

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

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 and 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

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

D37.1

Neoplasm of uncertain behavior of stomach

D37.8

Neoplasm of uncertain behavior of other specified digestive organs

D37.9

Neoplasm of uncertain behavior of digestive organ, unspecified

Z85.00

Personal history of malignant neoplasm of unspecified digestive organ

Z85.028

Personal history of other malignant neoplasm of stomach

Z85.038

Personal history of other malignant neoplasm of large intestine

Z85.068

Personal history of other malignant neoplasm of small intestine

Z85.118

Personal history of other malignant neoplasm of bronchus and lung

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), and 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): N(9)

NCD/LCD/LCA Document (s): A56660

https://www.cms.gov/medicare-coverage-database/search/article-date-search.aspx?DocID=A56660&bc=EAAAAAAAAAAA&SearchType=Advanced

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