Trodelvy (sacituzumab govitecan-hziy)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Sacituzumab govitecan, a trophoblast antigen-2 (Trop-2)-directed antibody-drug conjugate consisting of a humanized immunoglobulin G1 (IgG1) kappa monoclonal antibody (sacituzumab) covalently linked to a topoisomerase I inhibitor (SN-38), is an antineoplastic agent.
Sacituzumab govitecan, a trophoblast antigen-2 (Trop-2)-directed antibody-drug conjugate, is an antineoplastic agent. Trop-2 (also referred to as tumor-associated calcium signal transducer 2; TACS TD2) is an antigen expressed in various epithelial cancers, and has been associated with more aggressive tumors. The anti-Trop-2 antibody, a humanized immunoglobulin G1 (IgG1) kappa monoclonal antibody (sacituzumab), is covalently linked by a hydrolyzable linker to a topoisomerase I inhibitor (SN-38).
Following binding of the antibody to Trop-2-expressing cancer cells, the resultant complex is internalized by the cell. SN-38 is released via hydrolysis of the maleimide-containing crosslinker CL2A and also may be released extracellularly into the tumor microenvironment. SN-38 interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single-strand breaks.
The resulting DNA damage leads to apoptosis and cell death.
Sacituzumab govitecan has a high drug-to-antibody ratio (approximately 7-8 molecules of SN-38 are attached to each antibody molecule). Sacituzumab govitecan releases more than 90% of SN-38 over approximately 3 days. Plasma concentrations of sacituzumab govitecan are considerably higher than those of free SN-38, suggesting that the majority of SN-38 remains linked to the antibody while in circulation.
SN-38 is metabolized by UGT1A1 to the glucuronide metabolite SN-38G. Because SN-38 is less susceptible to inactivation via glucuronidation when bound to sacituzumab, the antibody-drug conjugate maintains SN-38 in its most active form until the antibody-drug conjugate binds to Trop-2; therefore, sacituzumab govitecan delivers higher concentrations of SN-38 to tumors compared with irinotecan-derived SN-38 therapy. In addition, the substantially lower plasma concentration of SN-38G achieved following administration of sacituzumab govitecan compared with administration of irinotecan may contribute to a lower incidence of severe diarrhea observed with sacituzumab govitecan.
The terminal half-lives of the antibody-drug conjugate and free SN-38 are 16 and 18 hours, respectively.
Population pharmacokinetic analyses indicate that age and race do not appear to have clinically important effects on the pharmacokinetics of the antibody-drug conjugate.
USES: This medication is used to treat certain types of breast cancer. It works by slowing or stopping the growth of cancer cells.
Generic name: sacituzumab govitecan-hziy
Pronunciation: (SAK-i-TOOZ-ue-mab GOE-vi-TEE-kan)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Trodelvy
Indications
The following indications are listed for Trodelvy:
- Hormone Receptor (Hr)-Positive, Her2-Negative Advanced Breast Cancer
- Metastatic Triple-Negative Breast Cancer
- Pd-L1 Expressing Triple-Negative Breast Cancer
Also known as: Er(-), Pr(-), Her-2(-) Metastatic Breast Cancer, Estrogen Receptor Negative, Progesterone Receptor Negative, Her-2 Negative Metastatic Breast Cancer, Hormone Receptor (Hr)-Negative, Her2-Negative Metastatic Breast Cancer, Hormone Receptor (Hr)-Negative, Her2-Negative, Pd-L1 Expressing Breast Cancer, Hormone Receptor (Hr)-Positive, Her2-Negative Metastatic Breast Cancer, Hr Negative, Her2 Negative, Pd-L1 Positive Breast Cancer, Hr-Positive, Human Epidermal Growth Factor Receptor 2 (Her2)-Negative Advanced Breast Cancer, Hr-Positive, Human Epidermal Growth Factor Receptor 2 (Her2)-Negative Metastatic Breast Cancer.
Dosing
Dosage of sacituzumab govitecan-hziy should be based on the patient's body weight prior to each cycle. If body weight changes by more than 10% compared with the previous dose, the dosage of sacituzumab govitecan-hziy may be adjusted more frequently during treatment cycles.
Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of sacituzumab govitecan-hziy may be necessary if adverse effects occur. In the IMMU-132-01 study, interruption of therapy was necessary in 45% of patients receiving sacituzumab govitecan-hziy; 1 or 2 dosage reductions were required in 24 or 9% of patients, respectively.
Dosage of sacituzumab govitecan-hziy should not be re-escalated following a dosage reduction.
Procedures for proper handling and disposal of antineoplastic agents should be followed.
Sacituzumab govitecan-hziy is administered by IV infusion only. The drug should not be administered by rapid IV injection, such as IV push or bolus. Following completion of the infusion, the IV line should be flushed with 20 mL of 0.9% sodium chloride injection.
Sacituzumab govitecan-hziy should not be mixed with or administered simultaneously through the same IV line with other drugs.
Unopened vials of sacituzumab govitecan-hziy powder for injection should be stored at 2-8degreesC and retained in the original carton to protect from light. Vials should not be frozen.
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Drug interactions
No formal drug interaction studies have been performed with sacituzumab govitecan or SN-38; however, the small-molecule component of sacituzumab govitecan, SN-38, undergoes conjugation by uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Sacituzumab govitecan is contraindicated in patients with known severe hypersensitivity reaction to the drug or any ingredient in the formulation. (See Hypersensitivity Reactions under Cautions.)
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 25% or more of patients with mTNBC treated with sacituzumab govitecan-hziy include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of sacituzumab govitecan-hziy have not been established in pediatric patients.
Sacituzumab govitecan can cause embryofetal mortality and/or teratogenicity if administered to a pregnant woman based on its mechanism of action. (See Fetal/Neonatal Morbidity and Mortality under Cautions)
It is not known whether sacituzumab govitecan or SN-38 is distributed into human milk. Because of the potential for serious adverse reactions to sacituzumab govitecan in breast-fed infants, women should be advised to discontinue nursing while receiving the drug and for 1 month after the last dose. The effects of the drug on breast-fed infants or on the production of milk are unknown.
The manufacturer makes no specific dosage recommendations for geriatric patients. (See Geriatric Use under Cautions)
In the IMMU-132-01 study, 18 or 35% of patients who received sacituzumab govitecan-hziy in the mTNBC cohort or total study population, respectively, were 65 years of age or older. No overall differences in safety and efficacy were observed between geriatric patients and younger adults.
Age does not appear to affect the pharmacokinetics of sacituzumab govitecan.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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