Coverage Policy Manual
Policy #: 2020020
Category: Pharmacy
Initiated: July 2020
Last Review: February 2024
  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 (e.g., 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).
 
Sacituzumab is indicated for the treatment of adult individuals 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.
 
Sacituzumab is indicated for the treatment of adult individuals with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.
 
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 individuals 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 individuals 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 individuals 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.   
 
On February 3, 2023, the Food and Drug Administration approved Sacituzumab govitecan-hziy for the treatment of adult individuals with unresectable locally advanced or metastatic hormone receptor (JR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
 
Coding
 
See CPT/HCPCS Code section below.

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.
 
Prior Approval is required for Sacituzumab govitecan-hziy (e.g., Trodelvy).
 
The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
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 February 14, 2024
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of sacituzumab govitecan-hziy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of adult individuals for the following:
 
1. Urothelial Cancer
a. Urothelial Carcinoma of the Prostate (NCCN 2A)
i. Therapy for metastatic disease as a single agent for:
1.  Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor;
2. Subsequent-line systemic therapy for individuals who received a first-line platinum-containing chemotherapy followed by avelumab maintenance therapy.
b. Primary Carcinoma of the Urethra (NCCN 2A)
i. Therapy for recurrent or metastatic disease as a single agent for:
1. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor;
2. Subsequent-line systemic therapy (individuals should have already received a platinum and a checkpoint inhibitor, if eligible)
c. Bladder Cancer (NCCN 2A)
i. Used as second-line Used as subsequent-line systemic therapy (if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor), or as subsequent-line systemic therapy (individuals should have already received platinum and a checkpoint inhibitor, if eligible) as a single agent for:
1. Stage II (cT2, N0) disease or stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status 2-3 months after primary treatment with concurrent bladder preserving chemoradiotherapy and maximal TURBT;
2. Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy;
3. Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy;
4. Stage IVA (any T, any N, M1a) disease if stable disease or progression following reassessment of tumor status after primary treatment with first-line systemic therapy;
5. Metastatic stage IVB (any T, any N, M1b) disease;
6. Muscle invasive local recurrence or persistent disease in a preserved bladder treated with curative intent;
7. Metastatic or local recurrence post cystectomy treated with curative intent.
d. Upper GU Tract Tumors (NCCN 2A)
i. Therapy for metastatic disease as a single agent for:
1. Second-line systemic therapy if a first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor was used, including maintenance checkpoint inhibitor;
2. Subsequent-line systemic therapy (individuals who should have already received a platinum, if eligible).
2. Breast Cancer
a. Invasive Breast Cancer (NCCN 1 for use as second-line therapy; NCCN 2A for all others)
i. Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer (TNBC) in individuals who have received at least two prior therapies, with at least one line for metastatic disease;
ii. Second-line therapy as a single agent for recurrent unresectable or stage IV triple-negative breast cancer (TNBC) in individuals who have received at least one prior regimen in the metastatic setting;
iii. Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for recurrent unresectable (local or regional) or stage IV (M1)hormone receptor positive and human epidermal growth factor receptor 2 (HER2)-negative cancers in individuals who have received prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy (including a taxane) at least one of which was in the metastatic setting , and if not a candidate for fam-trastuzumab deruxtecan-nxki.
b. Inflammatory Breast Cancer (NCCN 1 for use as second-line therapy; NCCN 2A for all others)
i. Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) hormone receptor positive and human epidermal growth factor receptor 2 (HER2)-negative cancers in individuals who have received prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy (including a taxane) at least one of which was in the metastatic setting and if not a candidate for fam-trastuzumab deruxtecan-nxki;
ii. Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for individuals with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer (TNBC) in individuals who have received at least one prior regimen in the metastatic setting;
3. Must be dosed in accordance with the FDA label.
 
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
Dosing per FDA Guidelines
 
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, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of sacituzumab govitecan-hziy for any indication or condition  not described above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective February 15, 2023 to February 13, 2024
 
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 individuals for the following:
 
1.  Bladder Cancer
 
a.  Urothelial Carcinoma of the Prostate (NCCN 2A)
i.  Therapy for metastatic disease as a single agent for subsequent-line systemic therapy for individuals who received a first-line platinum-containing chemotherapy followed by avelumab maintenance therapy
 
b.  Primary Carcinoma of the Urethra (NCCN 2A)
i.  Used as a single agent for recurrent or metastatic disease as subsequent-line systemic therapy for patients who received a first-line platinum-containing chemotherapy followed by avelumab maintenance therapy
 
c.   Bladder Cancer (NCCN 2A)
i.   Used as subsequent-line systemic therapy (patients should have already received platinum and a checkpoint inhibitor, if eligible) as a single agent for patients who received first-line platinum-containing chemotherapy followed by avelumab maintenance therapy for:
1.   Stage II (cT2, N0) disease or stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status 2-3 months after primary treatment with concurrent bladder preserving chemoradiotherapy and maximal TURBT
2.   Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy
3.   Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy
4.   Stage IVA (any T, any N, M1a) disease if stable disease or progression following reassessment of tumor status after primary treatment with first-line systemic therapy
5.   Metastatic stage IVB (any T, any N, M1b) disease
6.   Muscle invasive local recurrence or persistent disease in a preserved bladder treated with curative intent
7.   Metastatic or local recurrence post cystectomy treated with curative intent
 
d. Upper GU Tract Tumors (NCCN 2A)
i.  Therapy for metastatic disease as a single agent for subsequent-line systemic therapy for patients who received a first-line platinum-containing chemotherapy followed by avelumab maintenance therapy
 
2.   Breast Cancer
 
a.  Invasive Breast Cancer (NCCN 1 for use as second-line therapy; NCCN 2A for all others)
i.  Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer (TNBC) in patients who have received at least two prior therapies, with at least one line for metastatic disease
ii.  Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for recurrent unresectable (local or regional) or stage IV (M1)hormone receptor positive and human epidermal growth factor receptor 2 (HER2)-negative cancers in patients who have received prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy (including a taxane) at least one of which was in the metastatic setting , and if not a candidate for fam-trastuzumab deruxtecan-nxki
 
b.  Inflammatory Breast Cancer (NCCN 1 for use as second-line therapy; NCCN 2A for all others)
i.  Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) hormone receptor positive and human epidermal growth factor receptor 2 (HER2)-negative cancers in patients who have received prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy (including a taxane) at least one of which was in the metastatic setting and if not a candidate for fam-trastuzumab deruxtecan-nxki
ii.  Second-line therapy (may be considered for a later line) as a single agent (preferred regimen) for patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer (TNBC) in patients who have received at least two prior therapies, with at least one line for metastatic disease
 
3. Must be dosed in accordance with the FDA label.
 
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
Dosing per FDA Guidelines
 
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 for any indication or circumstance does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of sacituzumab govitecan-hziy for any indication or condition  not described above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 2021 to February 14, 2023
 
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)
 
2023 Update
The efficacy of TRODELVY was evaluated in a multicenter, open label, randomized study (TROPiCS-02; NCT03901339) conducted in 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer whose disease has progressed after the following in any setting: a CDK 4/6 inhibitor, endocrine therapy, and a taxane; patients received at least two prior chemotherapies in the metastatic setting (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months).
 
Patients were randomized (1:1) to receive TRODELVY 10 mg/kg as an intravenous infusion on Days 1 and 8 of a 21-day cycle (n=272) or single agent chemotherapy (n=271). Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (n=130), vinorelbine (n=63), gemcitabine (n=56), or capecitabine (n=22). Randomization was stratified by the following factors: prior chemotherapy regimens for metastatic disease (2 vs. 3-4), visceral metastasis (Yes or No), and endocrine therapy in the metastatic setting for at least 6 months (Yes or No).
 
Patients were treated until disease progression or unacceptable toxicity. Administration of TRODELVY was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. The primary efficacy outcome measure was PFS as determined by BICR per RECIST v1.1. Additional efficacy measures included OS, ORR by BICR, and DOR by BICR.
 
The median age of patients in the study population was 56 years (range: 27–86 years), 26% of patients were 65 years or over. The majority of patients were female (99%); 67% were White, 4% were Black and 3% were Asian, and 26% were of unknown race. Patients received a median of 7 (range: 3 to 17) prior systemic regimens in any setting and 3 (range: 0 to 8) prior systemic chemotherapy regimens in the metastatic setting. Approximately 42% of patients had 2 prior chemotherapy regimens for treatment of metastatic disease compared to 58% of patients who had 3 to 4 prior chemotherapy regimens and all patients had an ECOG performance status of 0 (45%) or 1 (55%). Ninety-five percent of patients had visceral metastases. Most patients received endocrine therapy in the metastatic setting for 6 months (86%).
 
The major efficacy outcome measures included ORR and DOR.  ORR was noted in 27.7 % (95 % CI: 19.6 to 36.9) of patients with a complete response of 5.4% and a partial response of 22.3%. Thirty-one patients responded to Trodelvy therapy with a mediation DOR of 7.2 months (95 % CI: 4.7 to 8.6 months) (Immunomedics, 2021). TRODELVY demonstrated a statistically significant improvement in PFS and OS versus single agent chemotherapy. (FDA, 2023)
 
ASCENT trial was a multicenter, open-label, randomized study in which Bardia and colleagues (2021) evaluated the efficacy of Trodelvy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who had relapsed after at least two prior chemotherapies for breast cancer (one of which could be in the neoadjuvant or adjuvant setting in which progression occurred in a 12-month period).  The major efficacy outcome was progression-free survival. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with Trodelvy and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy. The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with Trodelvy and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy. Objective response in patients was noted as 35% with Trodelvy and 5% with chemotherapy. The occurrence of notable treatment-related adverse events of grade 3 or higher were neutropenia (51% with Trodelvy and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and < 1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). (Bardia A, Hurvitz SA, Tolaney SM, 2021)
 
Patients with HR+/HER2- metastatic breast cancer (MBC) whose cancers have progressed despite conventional therapies represent an unmet clinical need. Trop-2, a transmembrane calcium signal transducer, is highly expressed in MBC and plays a role in tumor growth and progression. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate comprising a Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan, via a unique hydrolyzable linker. SG has demonstrated promising activity in a Phase I/II IMMU-132-01 basket study in heavily pretreated solid tumors, including HR+/HER2- MBC. Registrational Phase III TROPiCS-02 study (NCT03901339) is described, evaluating SG versus treatment of physician's choice in HR+/HER2- MBC. (Rugo HS, Bardia A, Tolaney SM, 2020)
 
2024 Update
In a randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). Patients had confirmed HR+ and HER2- locally recurrent inoperable or metastatic breast cancer and had received at least one previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting and two to four previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival (previously reported and not included in this analysis), and secondary endpoints included overall survival, objective response rate (ORR), and patient-reported outcomes. Overall survival was assessed using stratified log-rank tests and Cox regression. Trop-2 expression was assessed in tumour tissue by immunohistochemistry. In the statistical testing hierarchy, ORR and patient-reported outcomes were tested sequentially if overall survival was significant. This study is registered with ClinicalTrials.gov, NCT03901339.
 
At the data cutoff date of July 1, 2022, 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group. With a 12·5-month (IQR 6·4-18·8) median follow-up, 390 deaths occurred among 543 patients. Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0-15·7] vs 11·2 months [10·1-12·7]; hazard ratio [HR] 0·79, 95% CI 0·65-0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups. ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients vs 38 [14%]; odds ratio 1·63 [95% CI 1·03-2·56]; p=0·035), as was time to deterioration of global health status and quality of life (median 4·3 months vs 3·0 months; HR 0·75 [0·61-0·92]; p=0·0059) and fatigue (median 2·2 months vs 1·4 months; HR 0·73 [0·60-0·89]; p=0·0021). The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment.
 
Sacituzumab govitecan demonstrated statistically significant and clinically meaningful benefit over chemotherapy, with a 3·2-month median overall survival improvement and a manageable safety profile. These data support sacituzumab govitecan as a new treatment option for patients with pretreated, endocrine-resistant HR+ and HER2- metastatic breast cancer. (Rugo HS, Bardia A, Marmé F, 2023)

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

References: Bardia A, Hurvitz SA, Tolaney SM, et.al.(2021) Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485. PMID: 33882206.

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/

National Comprehensive Cancer Network (NCCNA)(2023) National Comprehensive Cancer Network, Inc. 2023 Practice Guidelines in Oncology—Bladder Cancer v.1.2023. Available at https://www.nccn.org. Accessed February 13, 2023.

National Comprehensive Cancer Network (NCCNA)(2023) National Comprehensive Cancer Network, Inc. 2023 Practice Guidelines in Oncology—Breast Cancer v.2.2023. Available at https://www.nccn.org. Accessed February 13, 2023.

NCCN Drugs & Biologics Compendium® for Sacituzumab govitecan-hziy (e.g., Trodelvy), © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed [February 6, 2024]. To view the most recent and complete version of the Compendium, go online to NCCN.org.

Rugo HS, Bardia A, Marmé F, Cortés J, Schmid P, Loirat D, Trédan O, Ciruelos E, Dalenc F, Gómez Pardo P, Jhaveri KL, Delaney R, Valdez T, Wang H, Motwani M, Yoon OK, Verret W, Tolaney SM.(2023) Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Oct 21;402(10411):1423-1433. doi: 10.1016/S0140-6736(23)01245-X. Epub 2023 Aug 23. PMID: 37633306.

Rugo HS, Bardia A, Tolaney SM, Arteaga C, Cortes J, Sohn J, Marmé F, Hong Q, Delaney RJ, Hafeez A, André F, Schmid P.(2020) TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Future Oncol. 2020 Apr;16(12):705-715. doi: 10.2217/fon-2020-0163. Epub 2020 Mar 30. PMID: 32223649.

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.


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