Coverage Policy Manual
Policy #: 2020020
Category: Pharmacy
Initiated: July 2020
Last Review: July 2022
  Sacituzumab govitecan-hziy (e.g., Trodelvy™)

Description:
Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers in the United States and is most common among younger women. TNBC tumors lack expression of estrogen, progesterone, or human epidermal growth factor (HER2) receptors. This type of cancer is associated with an aggressive tumor biology and poor prognosis. There are limited therapies available for TNBC.
 
Sacituzumab govitecan-hziy is a Trop-2 targeted antibody and topoisomerase inhibitor conjugate. Trop-2 is a cell surface glycoprotein overexpressed in various types of cancerous tumors. It has little to no expression in normal tissue. In this drug conjugate, SN-38 (an active metabolite of irinotecan), a topoisomerase I inhibitor, is coupled to a Trop-2 monoclonal antibody hRS7 IgG1k through the cleavable CL2A linker. Upon binding to Trop-2, hRS7 is internalized and delivers SN-38 into the tumor cell. SN-38 is released both intracellularly and in the tumor microenvironment. Sacituzumab govitecan-hziy (TrodelvyTM) tumor bound cells are destroyed by intracellular uptake of SN-38 and adjacent tumor cells are destroyed by the extracellular release of SN-38 (Bardia 2019).
 
Regulatory Status
 
Sacituzumab govitecan-hziy (e.g., TrodelvyTM) was approved by the U.S. Food and Drug Administration (FDA) on April 22, 2020 for the treatment of adult patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease.  
 
On January 1, 2021 J9317 will be effective for Sacituzumab govitecan-hziy (e.g., Trodelvy™).  Services billed as of January 1, 2021and after will be expected to be billed with this code.
 
On April 7, 2021, the Food and Drug Administration approved  Sacituzumab govitecan-hziy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
 
On April 13, 2021, the Food and Drug Administration approved Sacituzumab govitecan-hziy for the treatment of adult patients with Locally advanced or metastatic urothelial cancer (cUC) who have previously received a platinum-continuing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.   

Policy/
Coverage:
Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
 
The initial use of this drug requires documentation of direct physician involvement and signature in the ordering and evaluation as documented in the medical records. Concurrent review will require continued evidence of appropriate physician involvement.  
 
Effective July 2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of sacituzumab govitecan-hziy meets primary coverage criteria for the treatment of adult patients with:
    1. Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received at least two or more prior therapies, at least one of them for metastatic disease when ALL of the following criteria are met (FDA 2020; NCCN 2A):
        • Must be ≥ 18 years of age or older; AND
        • Must have submitted documentation of metastatic triple negative breast cancer; AND
        • Must have received at least two prior therapies, at least one of them for metastatic disease; AND
        • ECOG performance status of 0 or 1.
 
2. Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-a (PD-a) or programmed death-ligand 1 (PD-L1) inhibitor (FDA 2020; NCCN 2A):
        • Must be > 18 years of age or older: AND
        • Must have submitted documentation of locally advanced unresectable or mUC; AND
        • Had disease progression following a platinum-containing regimen immune check point inhibitor (CPI) therapy; AND
        • ECOG performance status of 0 or 1.
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
        • 0 = Fully active, able to carry on all pre-disease performance without restriction
        • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work
        • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
        • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
        • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
        • 5 = Dead
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
 
The recommended dose of sacituzumab govitecan-hziy is 10mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Continue treatment until disease progression or unacceptable toxicity.
 
Sacituzumab govitecan-hziy is available as a 180mg lyophilized powder in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Sacituzumab govitecan-hziy does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, the use of sacituzumab govitecan-hziy in any other condition than listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective 7/1/2020 to June 2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of sacituzumab govitecan-hziy meets primary coverage criteria for the treatment of adult patients with metastatic triple-negative breast cancer who have received at least two prior therapies for metastatic disease when ALL of the following criteria are met:
    1. Must be ≥ 18 years of age or older
    2. Must have submitted documentation of metastatic triple negative breast cancer
    3. Must have received at least two prior therapies for metastatic breast cancer
    4. ECOG performance status of 0 or 1
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
 
The recommended dose of sacituzumab govitecan-hziy (TrodelvyTM) is 10mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Continue treatment until disease progression or unacceptable toxicity.
 
Sacituzumab govitecan-hziy (TrodelvyTM) is available as a 180mg lyophilized powder in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Sacituzumab govitecan-hziy (TrodelvyTM) does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, the use of sacituzumab govitecan-hziy (TrodelvyTM) in any other condition than listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:
Sacituzumab govitecan-hziy (TrodelvyTM) was approved for TNBC under accelerated approval based on tumor response rate and duration of response. Continued approval for TNBC will be contingent on verification of clinical benefit in confirmatory trials.
 
Sacituzumab govitecan-hziy (TrodelvyTM) is being studied in an open-label, single-arm, multicenter trial involving patients with various types of cancers who have each received prior treatment for metastatic disease. Sacituzumab govitecan-hziy (TrodelvyTM) was approved for mTNBC based on 108 patients with mTNBC. Inclusion criteria for this subset of patients included 18 years of age or older, TNBC confirmed by histology or cytology, refractory to or relapsed disease after at least two prior standard therapeutic regimens for advanced/metastatic TNBC, prior exposure to a taxane in localized or advanced/metastatic setting, ECOG performance score of 0 to 1, measurable disease by CT or MRI, adequate renal and hepatic function, and adequate hematology without ongoing transfusion support. All patients had to be at least 2 weeks beyond prior anti-cancer treatment and high dose systemic corticosteroids. Sacituzumab govitecan-hziy (TrodelvyTM) was administered at 10mg/kg on Days 1 and 8 of each 28-day cycle until disease progression or unacceptable toxicity. If the patient experienced a severe treatment-related adverse event, dose reductions of 25% were allowed on the first occurrence and of 50% on the second occurrence. Treatment discontinuation occurred at the third occurrence. Computed tomography (CT) and magnetic resonance imagining (MRI) were performed at baseline and at 8 week intervals while the patient received therapy.
 
The primary endpoint was the objective response rate according to Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to response, the duration of response for patients who had a response, the clinical benefit rate (complete or partial response or stable disease for at least 6 months), progression-free and overall survival, and safety.108 patients received a mean of 18.7 doses of sacituzumab govitecan-hziy (TrodelvyTM) or 9.6 cycles. The median duration of exposure was 5.1 months. 36 (33%) of the 108 patients responded to therapy, including a complete response in 3 patients. Of the 33.3% who responded to the therapy, the median time to response was 2 months and the median duration of response was 7.7 months. There were no meaningful differences in response rates according to patient age, the onset of metastatic disease, the number of previous therapies, or the presence or absence of visceral metastases. The median progression free survival was 5.5 months. The duration of treatment with sacituzumab govitecan-hziy (TrodelvyTM) was compared with that of previous anticancer treatments in the 108 patients included in the study. The median duration of treatment with sacituzumab govitecan-hziy (TrodelvyTM) was 5.1 months and the median duration of treatment with previous anticancer treatments was 2.5 months. Common adverse events included nausea, diarrhea, fatigue, neutropenia, and anemia. Adverse events leading to interruption of therapy occurred in 44% of the patients treated with sacituzumab govitecan-hziy (TrodelvyTM). Three patients discontinued treatment due to adverse events.
 
2021 Update
The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab
govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician’s choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes.
 
Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with
one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline.
 
Of 468 assessable patients, 290 had Trop-2 expression data [64% (n ¼ 151 SG) versus 60% (n ¼ 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n ¼ 149 SG) versus 61% (n ¼ 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations.
 
SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with
standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup. (Bardia A, Hurvitz SA, Tolaney SM, 2021)
 
A phase 1/2 single-group, multicenter trial involving patients with advanced epithelial cancers who received sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects was conducted. A total of 108 patients 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 end points included safety; the objective response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), which was assessed locally; the duration of response; the clinical benefit rate (defined as a complete or partial response or stable disease for at least 6 months); progression-free survival; and overall survival. Post hoc analyses determined the response rate and duration, which were assessed by blinded independent central review.
 
The 108 patients with triple-negative breast cancer had received a median of 3 previous therapies (range, 2 to 10). Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment because of adverse events. Grade 3 or 4 adverse events (in ≥10% of the patients) included anemia and neutropenia; 10 patients (9.3%) had febrile neutropenia. The response rate (3 complete and 33 partial responses) was 33.3% (95% confidence interval [CI], 24.6 to 43.1), and the median duration of response was 7.7 months (95% CI, 4.9 to 10.8); as assessed by independent central review, these values were 34.3% and 9.1 months, respectively. The clinical benefit rate was 45.4%. Median progression-free survival was 5.5 months (95% CI, 4.1 to 6.3), and overall survival was 13.0 months (95% CI, 11.2 to 13.7).
 
Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer. Myelotoxic effects were the main adverse reactions. (NCT01631552.) Bardia A, Mayer IA, Vahdat LT, 2019).
 
TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label, phase II, registrational study. Cohort 1 includes patients with locally advanced or unresectable or mUC who had progressed after prior PLT and CPI. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary outcome was centrally reviewed ORR; secondary outcomes were progression-free survival, OS, duration of response, and safety.
 
Cohort 1 included 113 patients (78% men; median age, 66 years; 66.4% visceral metastases; median of three [range, 1-8] prior therapies). At a median follow-up of 9.1 months, the ORR was 27% (31 of 113; 95% CI, 19.5 to 36.6); 77% had decrease in measurable disease. Median duration of response was 7.2 months (95% CI, 4.7 to 8.6 months), with median progression-free survival and OS of 5.4 months (95% CI, 3.5 to 7.2 months) and 10.9 months (95% CI, 9.0 to 13.8 months), respectively. Key grade ≥ 3 treatment-related adverse events included neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), and febrile neutropenia (10%), with 6% discontinuing treatment because of treatment-related adverse events.
 
SG is an active drug with a manageable safety profile with most common toxicities of neutropenia and diarrhea. SG has notable efficacy compared with historical controls in pretreated mUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population. (Tagawa ST, Balar AV, Petrylak DP, 2021)
 
2022 Update
Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline.
 
Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations.
 
SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup. (Bardia A, Tolaney SM, Punie K,et.al., 2021)

CPT/HCPCS:
C9066Injection, sacituzumab govitecan hziy, 10 mg
J3490Unclassified drugs
J3590Unclassified biologics
J9317Injection, sacituzumab govitecan-hziy, 2.5 mg

References: Bardia A, Mayer I.A., Diamond J.R., et al.(2017) Efficacy and Safety of Anti-Trop-2 Antibody Drug Conj Sacituzumab Govitecan (IMMU-132) in Heavily Pretreat Patients with MetaTripleNegative Breast Can. Journal of Clinical Oncology. 2017; Access 19 June 2020

Bardia A, Mayer I.A., Vahdat L.T., et al.(2019) Sacituzumab Govitecan-hziy in Refractory Metastatic Triple Negative Breast Cancer. N Engl J Med. 2019; Accessed 19 June 2020

Bardia A, Mayer IA, Vahdat LT, et.al.(2019) Sacituzumab Govitecan-hziy in Refractory Metastatic TripleNegative Breast Cancer. N Engl J Med. 2019 Feb 21;380(8):741-751. doi: 10.1056/NEJMoa1814213. PMID: 30786188.

Bardia A, Tolaney SM, Punie K, et.al.,(2021) Biomarker analyses in phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Ann Oncol. 2021 Sep;32(9):1148-1156. doi: 10.1016/j.annonc.2021.06.002. Epub 2021 Jun 8. PMID: 34116144.

National Comprehensive Cancer Network (NCCN).(2021) sacituzumab govitecan-hziy. NCCN Drugs & Biologics Compendium //www.nccn.org/professionals/drug_compendium/content/

Tagawa ST, Balar AV, Petrylak DP,(2021) TROPHY-U-01 A PhaseII OpenLabel Study Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Prog After PlatinumBased Chemo and Checkpoint Inhibitors. J Clin Oncol. 2021 Apr 30:JCO2003489. doi: 10.1200/JCO.20.03489. Epub ahead print. PMID: 33929895

TRODELVY (sacituzumab govitecan-hziy), package insert. Morris Plains, NJ. Immunomedics, Inc.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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