Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Sacituzumab govitecan-hziy (TrodelvyTM)

Policy #:08.01.60

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

HER2 PROTEIN EXPRESSION TESTING
Coverage of sacituzumab govitecan-hziy (TrodelvyTM) requires that HER2 protein expression is verified as a negative result by one of the following FDA-approved diagnostic tests:
  • Immunohistochemical (IHC) assay with a result of 0 to 1+
  • Fluorescence in situ hybridization (FISH) test (lower than 1.8)
  • Single-probe in situ hybridization (ISH) test with average HER2 copy number less than 4.0 signals/cell
  • Dual-probe ISH test HER2/CEP17 (chromosome enumeration probe 17) ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell

Confirmatory tests should be performed for borderline results as follows:
  • If IHC assay has a result of 2+, confirm with ISH test of the same sample or a new test with IHC or ISH (if new sample available).
  • If FISH test has a HER2 gene/chromosome 17 ratio of 1.8-2.0, confirm with FISH re-test; additional cell counting and recalculation of the ratio; or IHC assay.
  • If single-probe ISH assay has an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
  • If dual-probe ISH assay has a HER2/CEP17 ratio less than 2.0 and an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

SACITUZUMAB GOVITECAN-HZIY (TrodelvyTM)
Sacituzumab govitecan-hziy (TrodelvyTM) injection is considered medically necessary and, therefore, covered as monotherapy when the following criteria are met:
  • The individual has metastatic triple-negative (estrogen receptor [ER- ] / progesterone receptor [PR-] / human epidermal growth factor receptor 2 [HER2-]) breast cancer (mTNBC) based on most recently analyzed biopsy.
  • The individual has received at least two prior therapies for metastatic disease, including prior taxane (e.g., Paclitaxel [Taxol] or docetaxel [Taxotere]).

CONTINUATION THERAPY
Sacituzumab govitecan-hziy (TrodelvyTM) is considered medically necessary and, therefore, covered for continuation therapy until disease progression, drug intolerance, or unacceptable toxicity.

NOT MEDICALLY NECESSARY

When FDA-approved diagnostic tests do not reveal triple-negative (ER-/PR-/HER2-) breast cancer, sacituzumab govitecan-hziy (TrodelvyTM) is considered not medically necessary and, therefore, not covered because the available published peer-reviewed literature does not support their use in the treatment of those diseases.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for sacituzumab govitecan-hziy (TrodelvyTM) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

DRUG INFORMATION

In accordance with US Food and Drug Administration (FDA) prescribing information, sacituzumab govitecan-hziy (TrodelvyTM) is administered 10 mg/kg intravenously on days 1 and 8 of continuous 21-day treatment cycles.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, sacituzumab govitecan-hziy (TrodelvyTM ) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Sacituzumab govitecan-hziy (TrodelvyTM) was approved by the FDA on April 22, 2020 for the treatment of of adult individuals with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. The safety and effectiveness have not been established in pediatric individuals.
Description

Sacituzumab govitecan-hziy (TrodelvyTM) is a trophoblast cell-surface antigen 2 (Trop-2) directed antibody and topoisomerase inhibitor conjugate, composed of the following three components: the humanized monoclonal antibody, hRS7 IgG1 (also called sacituzumab), which binds to Trop-2 (the trophoblast cell-surface antigen-2); the drug SN-38, a topoisomerase inhibitor; a hydrolysable linker (called CL2A), which links the humanized monoclonal antibody to SN-38. The cytotoxic component of sacituzumab govitecan-hziy is SN-38, a highly potent topoisomerase I inhibitor and metabolite of irinotecan. The cytotoxic activity of SN-38 delivered through sacituzumab govitecan-hziy is 100 to 1000 times as high as that of irinotecan. The recombinant monoclonal antibody is produced by mammalian (murine myeloma) cells, while the small molecule components SN-38 and CL2A are produced by chemical synthesis. Sacituzumab govitecan-hziy contains on average 7 to 8 molecules of SN-38 per antibody molecule. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors.

Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers. TNBC lack receptors for estrogen, progesterone, and HER2 and don’t respond to drugs that target estrogen, progesterone, or HER2 receptors. Triple-negative breast cancer differs from other types of invasive breast cancer in that they grow and spread faster, have limited treatment options, and a worse prognosis. These cancers tend to be more common in women younger than age 40, who are African-American, or who have a BRCA1 mutation.

DIAGNOSTIC TESTS FOR HER2 PROTEIN EXPRESSION TESTING

HER2 protein overexpression is detected either by immunohistochemical (IHC) assay that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample or with a type of in situ hybridization (ISH) test for gene amplification (e.g., fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], dual in situ hybridization [DISH]). The FDA has approved several commercially available tests to aid in the selection of breast cancer individuals for fam-trastuzumab deruxtecan-nxki (Enhertu®) therapy. The National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) guidelines (2018) further recommend that IHC assay and ISH testing should only be done at laboratories that are accredited to perform HER2 testing.

  • An IHC test result is reported as 0 or 1+ (negative), 2+ (borderline), or 3+ (positive).
  • A FISH test result is reported as a HER2 gene/chromosome 17 ratio less than 1.8 (negative), a ratio of 1.8 to less than 2.0 (borderline), or a ratio of 2.0 or greater (positive).
  • A single-probe ISH test result is reported as: average HER2 copy number less than 4.0 signals/cell (negative); 4.0 to less than 6.0 signals/cell (borderline); 6.0 or greater signals/cell (positive).
  • A dual-probe ISH test result is reported as HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater (positive); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell (negative); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 4.0 to less than 6.0 signals/cell (borderline); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater (positive).

The NCCN and ASCO both have issued guidelines for HER2 testing in invasive breast cancer that call for confirming a borderline or equivocal result:
  • IHC assay result of 2+: confirm with ISH test (if same sample), or with a new IHC or ISH test (if new sample available).
  • FISH assay: confirm with either a repeat FISH test or an additional cell counting and recalculation of the ratio. If a repeat FISH test remains equivocal, an IHC assay is recommended for confirmation.
  • Single-probe ISH assay: confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
  • Dual-probe ISH assay: confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).
PEER-REVIEWED LITERATURE

SUMMARY
Sacituzumab govitecan-hziy (TrodelvyTM) was evaluated in a phase 1/2 open label, single-group, multicenter trial involving individuals with advanced epithelial cancers.

A total of 108 individuals received sacituzumab govitecan-hziy at a dose of 10 mg per kilogram of body weight after receiving at least two previous anticancer therapies for metastatic triple-negative breast cancer. The primary efficacy end point was the objective response rate. The secondary end points were the time to response and the duration of response and progression-free and overall survival. Safety evaluations included assessments of adverse events, change in a laboratory values, vital signs, physical examination, and 12-lead electrocardiography (ECG). The response rate was 33.3% (36 of 108 individuals), including complete responses in 3 individuals (2.8%). The clinical benefit rate (including stable disease for at least 6 months) was 45.4% (49 of 108 individuals). At the time of data cutoff, 94 individuals (87.0%) had disease progression and 77 individuals (71.3%) had died. The median progression-free survival was 5.5 months (95% CI, 4.1 to 6.3); the estimated probability of progression-free survival was 41.9% at 6 months and 15.1% at 12 months. The median overall survival was 13.0 months (95% CI, 11.2 to 13.7); the estimated probability of survival was 78.5% at 6 months and 51.3% at 12 months. Among individuals with metastatic triple-negative breast cancer who had received at least two previous therapies for metastatic disease (median, three) and who received treatment with sacituzumab govitecan-hziy, the response rate was 33.3%, the median duration of response was 7.7 months, the median progression-free survival was 5.5 months, and the median overall survival was 13.0 months. The duration of treatment with sacituzumab govitecan-hziy was longer than with the immediate previous antitumor therapy (5.1 months vs. 2.5 months).

The most common adverse events were nausea, diarrhea, fatigue, neutropenia, and anemia, and the most common adverse events of grade 3 or higher (>5% incidence) included neutropenia, anemia, and a decreased white-cell count.

CONFIRMATORY TRIAL

A confirmatory multicenter, randomized, phase 3 trial (ASCENT; ClinicalTrials.gov number, NCT02574455) is currently recruiting individuals to compare sacituzumab govitecan-hziy with the provider’s choice of four single-agent types of chemotherapy (capecitabine, gemcitabine, vinorelbine, and eribulin) in individuals with metastatic triple-negative breast cancer that is refractory or relapsed after at least two previous forms of chemotherapy (including a taxane).

OFF-LABEL INDICATION


There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.


References

American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP). Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Clinical Practice Guideline Update. [CAP Web site]. 05/2020. Available at: https://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2019-0904-SA. Accessed May 06, 2020.

Bardia A , Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. New Engl J Med.2019;380:741-51.

ClinicalTrials.gov. Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers. ClinicalTrials.gov Identifier: NCT01631552. First Posted: June 29, 2012; Last Update Posted: November 22, 2019. Available at: https://clinicaltrials.gov/ct2/show/record/NCT01631552. Accessed May 06, 2020.

ClinicalTrials.gov. ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT). ClinicalTrials.gov Identifier: NCT02574455. First Posted: October 12, 2015; Last Update Posted: February 11, 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02574455 . Accessed May 06, 2020.

Elsevier’s Clinical Pharmacology Compendium .Sacituzumab govitecan-hziy (TrodelvyTM).[Clinical Key Web site]. 04/28/20. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed May 06, 2020.

Lexi-Drugs Compendium. Sacituzumab govitecan-hziy. [Lexicomp Online Web site]. 05/05/2020. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed May 06, 2020.

Sacituzumab govitecan-hziy (TrodelvyTM) [prescribing information]. Morris Plains, NJ: Immunomedics, Inc.; 2020. Available at: https://trodelvy.com/prescribing-information. Accessed May 06, 2020.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Sacituzumab govitecan-hziy (TrodelvyTM). Greenwood Village, CO. [Micromedex® Solutions Web site]. 04/23/2020. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed May 06, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Sacituzumab govitecan-hziy (TrodelvyTM). [FDA Web site]. Original: 04/22/20. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm . Accessed May 06, 2020.

US Food and Drug Administration (FDA). Devices @ FDA (HER2). Available at: http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm. Accessed April 17, 2019.

US Food and Drug Administration (FDA). Fam-trastuzumab deruxtecan-nxki (Enhertu ®) prescribing information & approval letter. [FDA Web site]. 04/2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf. Accessed May 06, 2020.




Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)




Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)



N/A



Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See attachment A


HCPCS Level II Code Number(s)



THE FOLLOWING CODE(S) ARE USED TO REPRESENT SACITUZUMAB GOVITECAN-HZIY (TRODELVYTM)

C9399 Unclassified drugs or biologicals

J3590 Unclassified biologics


Revenue Code Number(s)



N/A



Misc Code

N/A:


N/A



Coding and Billing Requirements


Cross References

Attachment A: Sacituzumab govitecan-hziy (TrodelvyTM)
Description: Diagnosis list




Policy History

08.01.60
06/22/2020This version of the policy will become effective 06/22/2020.

This new policy has been developed to communicate the Company’s coverage criteria for sacituzumab govitecan-hziy (TrodelvyTM), including dosing and frequency.
Version Effective Date: 06/22/2020
Version Issued Date: 06/22/2020
Version Reissued Date: N/A

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