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.1, 2, 4, 5, 6, 12, 14
Sacituzumab govitecan-hziy is used for the treatment of metastatic triple-negative (i.e., estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor type 2 [HER2]-negative) breast cancer (mTNBC) previously treated with at least 2 therapies for metastatic disease.1, 3, 4, 8, 9 The accelerated approval of sacituzumab govitecan-hziy is based on tumor response rate and duration of response;1, 14 continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1, 8
The current indication for sacituzumab govitecan-hziy is based principally on the results for a cohort of 108 adults with metastatic triple-negative breast cancer (mTNBC) previously treated with at least 2 therapies for metastatic disease in a multicenter, phase 1/2, single-arm trial (IMMU-132-01).1, 4, 8 In this study, patients received sacituzumab govitecan-hziy 10 mg/kg as an IV infusion on days 1 and 8 of each 21-day cycle.1, 4 Treatment was continued until disease progression or unacceptable toxicity occurred.1, 4 The primary measure of efficacy was objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1); additional outcome measures included duration of response and progression-free and overall survival.1, 4 The median age of patients in the mTNBC cohort was 55 years; 76% of patients were White, 7% were Black, 99% were female, 76% had visceral disease, 42% had hepatic metastases, 56% had lung/pleura metastases, and 2% had brain metastases.1, 4 Twelve patients (11%) had Stage IV disease at the time of initial diagnosis.1 In the mTNBC cohort, patients had received a median of 3 prior systemic therapies in the metastatic setting.1, 4 Most patients (98%) with mTNBC received prior therapy with taxanes and 86% received anthracyclines either in the neoadjuvant or metastatic setting.1, 4 This study excluded patients with known Gilbert syndrome.1, 8 Patients with known brain metastases were initially excluded from the trial; however, the protocol was later amended to allow enrollment of patients with stable brain metastases who did not require high-dose corticosteroid therapy (e.g., more than 20 mg of prednisone or equivalent) for at least 4 weeks.1, 8 Objective response rate in patients receiving sacituzumab govitecan-hziy was 33%, with a complete response in 2.8% of patients.1, 4 The median duration of response was 7.7 months and 56% of the patients who responded to sacituzumab govitecan-hziy had durable responses of 6 months or more.1, 4 Median progression-free survival was 5.5 months and median overall survival was 13 months.4
In a confirmatory phase 3 randomized controlled trial (ASCENT), 468 patients with relapsed or refractory mTNBC without brain involvement who had previously received at least 2 chemotherapies (including therapy with a taxane) in the advanced or metastatic setting were randomized to receive sacituzumab govitecan-hziy 10 mg/kg administered by IV infusion on days 1 and 8 of each 21-day cycle or a single-agent treatment of the clinician's choice (i.e., capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression or unacceptable toxicity occurred.9 The primary measure of efficacy was progression-free survival according to the RECIST 1.1 as assessed by a central review committee.9 In this study, the median age of patients was 54 years and patients had received a median of 4 prior therapies.9 Median progression-free survival (5.6 versus 1.7 months) and overall survival (12.1 versus 6.7 months) were prolonged in patients receiving sacituzumab govitecan-hziy compared with those receiving standard single-agent therapy.9 Objective response rate also was higher in patients receiving sacituzumab govitecan-hziy compared with those receiving standard single-agent therapy (35 versus 5%).9
Sacituzumab govitecan should not be substituted for or used with other drugs containing irinotecan or its active metabolite SN-38.1
Because infusion or hypersensitivity reactions may occur with sacituzumab govitecan, patients should be closely observed during infusions and for at least 30 minutes following completion of the infusion.1 Premedication with an antipyretic, a histamine H1-receptor antagonist, and a histamine H2-receptor antagonist is recommended prior to each infusion.1 If an infusion-related reaction occurs, corticosteroids may be considered for subsequent infusions.1 Sacituzumab govitecan should be administered in settings where emergency equipment and appropriate medical support are available for the management of potential infusion-related or hypersensitivity reactions.1 (See Hypersensitivity Reactions under Cautions.)
Because sacituzumab govitecan is moderately emetogenic,1, 4, 6 premedication with a 2- or 3-drug antiemetic regimen (e.g., dexamethasone with either a type 3 serotonin [5-HT3] receptor antagonist or a neurokinin-1 [NK1] receptor antagonist, and other drugs as indicated) is recommended prior to each dose of sacituzumab govitecan.1
Because neutropenia occurs frequently during sacituzumab govitecan therapy, the manufacturer states that secondary prophylaxis with a granulocyte colony-stimulating factor (G-CSF) should be considered.1
Procedures for proper handling and disposal of antineoplastic agents should be followed.1
Sacituzumab govitecan-hziy is administered by IV infusion only.1 The drug should not be administered by rapid IV injection, such as IV push or bolus.1 Following completion of the infusion, the IV line should be flushed with 20 mL of 0.9% sodium chloride injection.1
Sacituzumab govitecan-hziy should not be mixed with or administered simultaneously through the same IV line with other drugs.1
Unopened vials of sacituzumab govitecan-hziy powder for injection should be stored at 2-8°C and retained in the original carton to protect from light.1 Vials should not be frozen.1
Prior to administration, commercially available sacituzumab govitecan-hziy lyophilized powder for injection must be reconstituted and diluted.1 The appropriate number of vials containing sacituzumab govitecan-hziy should be removed from the refrigerator and allowed to reach room temperature.1 The powder for injection is reconstituted by adding 20 mL of 0.9% sodium chloride injection to a vial labeled as containing 180 mg of the drug to provide a solution containing 10 mg/mL.1 The vial should be gently swirled and allowed to sit until complete dissolution occurs (e.g., up to 15 minutes); the resulting solution should not be shaken.1 The reconstituted solution should be inspected visually for particulate matter and discoloration prior to dilution. 1 The reconstituted solution should be clear and yellow, and free of visible particulates.1 The reconstituted solution should be used immediately to prepare a diluted solution for infusion.1
Prior to administration, the required amount of reconstituted sacituzumab govitecan-hziy solution must be diluted in only 0.9% sodium chloride injection to provide a final solution with a sacituzumab govitecan-hziy concentration of 1.1-3.4 mg/mL in a total volume of no more than 500 mL (i.e., if a 500-mL infusion bag of 0.9% sodium chloride injection is used, a volume of diluent equal to the total required volume of reconstituted sacituzumab govitecan solution should be removed from the infusion bag prior to addition of the reconstituted solution).1 The manufacturer states that the drug must be diluted in a polypropylene infusion bag.1 The reconstituted solution should be slowly injected into the infusion bag to minimize foaming.1 The final diluted solution for infusion should not be shaken.1 Any unused portions in the vials should be discarded.1
For patients weighing more than 170 kg, the total dose of sacituzumab govitecan-hziy should be divided equally between two 500-mL infusion bags and infused sequentially.1 If immediate administration of the diluted solution is not possible, the solution may be stored at 2-8°C for up to 4 hours; following removal from refrigeration, the diluted solution for infusion must be administered within 4 hours (including infusion time).1 Diluted solutions of the drug must be protected from light.1
The initial sacituzumab govitecan-hziy infusion should be administered IV over 3 hours.1
Subsequent infusions of the drug should be administered over 1-2 hours if infusion-related reactions did not occur during the previous infusion.1
Dosage of sacituzumab govitecan-hziy should be based on the patient's body weight prior to each cycle.1 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.1
For the treatment of previously treated metastatic triple-negative breast cancer in adults, the recommended adult dosage of sacituzumab govitecan-hziy is 10 mg/kg administered as an IV infusion on days 1 and 8 of each 21-day treatment cycle.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1 Sacituzumab govitecan-hziy should not be administered at a dosage exceeding 10 mg/kg.1
Dosage Modification for Toxicity
Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of sacituzumab govitecan-hziy may be necessary if adverse effects occur.1 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.1
Dosage of sacituzumab govitecan-hziy should not be re-escalated following a dosage reduction.1
For absolute neutrophil count (ANC) below 1500/mm3 on day 1 of any cycle, ANC below 1000/mm3 on day 8 of any cycle, or febrile neutropenia, sacituzumab govitecan therapy should be withheld.1
For the first occurrence of grade 4 neutropenia lasting 7 or more days, grade 3 febrile neutropenia (ANC less than 1000/mm3 and fever 38.5°C or higher), or grade 3 or 4 neutropenia that delays scheduled dosing by 2 or 3 weeks until recovery to grade 1 or less, the dosage of sacituzumab govitecan should be reduced by 25% and G-CSF therapy should be initiated.1
If these neutropenic events recur following a 25% reduction in dosage, the dosage of sacituzumab govitecan should be reduced by 50%.1
If these neutropenic events recur following a 50% reduction in dosage or if grade 3 or 4 neutropenia delays scheduled dosing beyond 3 weeks until recovery to grade 1 or less, treatment with sacituzumab govitecan should be discontinued.1
For other grade 3 or 4 hematologic toxicities that do not recover to grade 1 or less within 3 weeks, treatment with sacituzumab govitecan should be discontinued.1
If grade 3 or 4 nausea, vomiting, or diarrhea occurs, sacituzumab govitecan therapy should be withheld until the toxicity improves to grade 1 or less.1
For the first occurrence of grade 3 or 4 nausea, vomiting, or diarrhea that persists despite antiemetic or antidiarrheal therapy, sacituzumab govitecan therapy should be withheld until the toxicity improves to grade 1 or less, and then may be resumed with a 25% reduction in dosage. 1
For the second occurrence of grade 3 or 4 nausea, vomiting, or diarrhea that persists despite antiemetic or antidiarrheal therapy, sacituzumab govitecan therapy should be withheld until the toxicity improves to grade 1 or less, and then may be resumed at a dosage reduced by 50%.1
For the third occurrence of grade 3 or 4 nausea, vomiting, or diarrhea that persists despite antiemetic or antidiarrheal therapy, treatment with sacituzumab govitecan should be discontinued.1
For the first occurrence of grade 4 nonhematologic toxicity of any duration or grade 3 or 4 nonhematologic toxicity persisting for longer than 48 hours despite optimal medical management, or grade 3 or 4 nonhematologic toxicity that delays scheduled dosing by 2 or 3 weeks until recovery to grade 1 or less, the dosage of sacituzumab govitecan should be reduced by 25%.1
If such nonhematologic effects recur following a 25% reduction in dosage, the dosage of sacituzumab govitecan should be reduced by 50%.1
If such nonhematologic effects recur following a 50% reduction in dosage, treatment with sacituzumab govitecan should be discontinued.1
For grade 3 or 4 nonhematologic toxicity that does not recover to grade 1 or less within 3 weeks, treatment with sacituzumab govitecan should be discontinued.1
If an infusion-related reaction occurs, the infusion should be interrupted or the infusion rate should be reduced.1 If life-threatening infusion-related reactions occur, sacituzumab govitecan therapy should be permanently discontinued.1
In patients with mild hepatic impairment (serum bilirubin concentration not exceeding the upper limit of normal [ULN] and AST concentration exceeding the ULN, or serum bilirubin concentration exceeding the ULN, but no more than 1.5 times the ULN and any AST concentration), no initial dosage adjustment is necessary.1
The safety of sacituzumab govitecan-hziy in patients with moderate or severe hepatic impairment has not been established; therefore, the manufacturer makes no specific dosage recommendations for such patients.1 (See Hepatic Impairment under Cautions)
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1 (See Renal Impairment under Cautions)
The manufacturer makes no specific dosage recommendations for geriatric patients.1 (See Geriatric Use under Cautions)
Pharmacogenomic Dosage Considerations
Patients who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele have an increased risk of neutropenia and other toxicities.1 The manufacturer states that an appropriate dosage for patients who are homozygous for UGT1A1*28 has not been established; therefore, such patients should be closely monitored for severe neutropenia and managed based on individual patient tolerance.1 (See Pharmacogenomic Considerations under Cautions.)
In the IMMU-132-01 study, patients with known Gilbert syndrome were excluded since this condition is associated with UGT1A1 deficiency.1, 8
Sacituzumab govitecan is contraindicated in patients with known severe hypersensitivity reaction to the drug or any ingredient in the formulation.1 (See Hypersensitivity Reactions under Cautions.)
Severe or life-threatening neutropenia may occur during sacituzumab govitecan therapy.1 In the IMMU-132-01 study, neutropenia of any grade occurred in 64% of patients with metastatic triple-negative breast cancer (mTNBC) receiving sacituzumab govitecan-hziy and in 54% of the total study population. 1, 4 In the total study population, grade 4 neutropenia was reported in 13% of patients receiving the drug.1 Febrile neutropenia occurred in 6% of the total study population, including 8% of patients with mTNBC receiving the drug.1 Permanent discontinuance of therapy due to neutropenia or febrile neutropenia was necessary in less than 1% of the total study population.1 Neutropenia was the most common reason for treatment interruption and dosage reduction. 1, 4
Complete blood cell (CBC) counts should be monitored periodically during therapy.1 The manufacturer states that secondary prophylaxis with a granulocyte colony-stimulating factor (G-CSF) should be considered.1 If neutropenia occurs, temporary interruption of therapy, dosage reduction, or discontinuance of the drug may be required.1 (See Dosage Modification for Toxicity under Dosage and Administration.) If febrile neutropenia occurs, anti-infective therapy should be promptly initiated.1
Severe diarrhea may occur during sacituzumab govitecan therapy.1 Clinical experience suggests diarrhea typically occurs within the first few days of therapy.5 In the IMMU-132-01 study, diarrhea occurred in 63% of patients with mTNBC receiving sacituzumab govitecan-hziy and in 62% of the total study population.1 Grade 3 or 4 diarrhea occurred in 9% of patients with mTNBC and in 9% of the total study population.1 Neutropenic colitis occurred in 2% of patients with mTNBC and in 1% of the total study population.1 Discontinuance of therapy was necessary because of diarrhea in less than 1% of the total study population.1
If diarrhea occurs, patients should receive appropriate therapy (e.g., antidiarrheal agents, fluid replacement) if necessary.1 If early diarrhea of any severity occurs, the manufacturer recommends therapy with atropine as appropriate.1 At the onset of late diarrhea, patients should be evaluated for infectious causes; if an infectious etiology is ruled out, loperamide should be initiated at a dosage of 4 mg initially, followed by 2 mg with every episode of diarrhea up to a maximum of 16 mg daily.1 Loperamide should be discontinued 12 hours after diarrhea resolves.1 If an excessive cholinergic response (e.g., abdominal cramping, diarrhea, salivation) occurs, premedication with appropriate therapy (e.g., atropine) may be used prior to subsequent infusions.1 Temporary interruption, dosage reduction, or permanent discontinuance of therapy may be necessary if diarrhea occurs.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
Other Warnings and Precautions
Severe or life-threatening hypersensitivity reactions and anaphylaxis have been reported during therapy with sacituzumab govitecan.1 In the IMMU-132-01 study, grade 3 or 4 hypersensitivity reactions occurred in 3% of patients with mTNBC receiving sacituzumab govitecan-hziy 4 and in 1% of the total study population.1 Hypersensitivity reactions occurred within 24 hours of sacituzumab govitecan dosing in 37% of the total study population.1 Permanent discontinuance of sacituzumab govitecan-hziy due to hypersensitivity reactions was necessary in 1% of the total study population.1
Patients should be closely observed during infusions and for at least 30 minutes following completion of sacituzumab govitecan infusions.1 Premedication with an antipyretic, a histamine H1-receptor antagonist, and a histamine H2-receptor antagonist is recommended prior to each infusion of sacituzumab govitecan.1 (See General under Dosage and Administration.)
Sacituzumab govitecan has moderate emetogenic potential.1, 4, 6 In the IMMU-132-01 study, the incidence of nausea in the mTNBC cohort was similar to the incidence in the total study population (69%); grade 3 nausea occurred in 6 or 5% of patients in these respective groups.1 Vomiting occurred in 49 or 45% of patients in the mTNBC cohort or the total study population, respectively; grade 3 vomiting occurred in 6 or 4% of patients in these respective groups.1
Because sacituzumab govitecan is moderately emetogenic,1, 4, 6 premedication with a 2- or 3-drug antiemetic regimen is recommended prior to each dose of sacituzumab govitecan.1 (See General under Dosage and Administration.) Temporary interruption of therapy, dosage reduction, or permanent discontinuance of therapy may be necessary if nausea or vomiting occurs.1 (See Dosage Modification for Toxicity under Dosage and Administration.)
Pharmacogenomic Considerations
Genetic variants of the UGT1A1 gene, such as the UGT1A1*28 allele, may result in reduced UGT1A1 enzyme activity. 1 The small-molecule component (SN-38) of the antibody-drug conjugate is metabolized via UGT1A1; therefore, individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia and other adverse reactions.1 Approximately 20, 10, and 2% of Blacks, Whites, and East Asians are homozygous for the UGT1A1*28 allele.1, 14 Decreased-function alleles other than UGT1A1*28 may be present in certain populations.1
Among patients who received sacituzumab govitecan-hziy in the IMMU-132-01 study and had retrospective UGT1A1 genotyping results available, 45, 43, or 11% were heterozygous for the UGT1A1*28 allele, homozygous for the wild-type allele, or homozygous for the UGT1A1*28 allele, respectively; grade 4 neutropenia occurred in 13, 11, or 26% of patients in these respective groups.1 In a phase 1/2 trial, grade 3 or greater neutropenia occurred more frequently in patients with homozygous UGT1A1*28 allele haplotype compared with those with homozygous wild-type allele or heterozygous UGT1A1*28 allele haplotypes; however, no significant correlation between the 3 haplotypes and severe neutropenia for the combined dose groups (8 or 10 mg/kg on day 1 and 8 of each 21-day cycle) within the first 2 cycles or at any time during treatment was observed.12
In the IMMU-132-01 study, patients with known Gilbert syndrome were excluded since this condition is associated with UGT1A1 deficiency.1, 8
The manufacturer makes no specific recommendations for screening for UGT1A1 genetic variants prior to initiating therapy with sacituzumab govitecan; however, some clinicians state that management of a neutropenic event is more appropriate than screening for UGT1A1 genetic variants.1, 12 The appropriate dose for patients who are homozygous for UGT1A1*28 has not been established; therefore, such patients should be closely monitored for severe neutropenia and managed based on individual patient tolerance.1
Fetal/Neonatal Morbidity and Mortality
There are no available data regarding the risk of sacituzumab govitecan use in pregnant women; however, based on its mechanism of action, the drug may cause embryofetal mortality and/or teratogenicity.1 The SN-38 component of sacituzumab govitecan is genotoxic and toxic to rapidly dividing cells.1
Pregnancy should be avoided during sacituzumab govitecan therapy.1 The manufacturer states that a pregnancy test should be performed prior to initiation of sacituzumab govitecan, and females of reproductive potential should be advised to use effective contraceptive methods during therapy and for 6 months after the last dose.1 In addition, men with such female partners should be advised to use effective methods of contraception during therapy and for 3 months after the last dose.1 Patients should be apprised of the potential hazard to the fetus if sacituzumab govitecan is used during pregnancy.1
Based on findings in animals, sacituzumab govitecan may impair fertility in females.1
There is a potential for immunogenicity with sacituzumab govitecan.1 Persistent anti-sacituzumab govitecan antibodies developed in 2 of 106 patients with mTNBC in the IMMU-132-01 study.1
Sacituzumab govitecan can cause embryofetal mortality and/or teratogenicity if administered to a pregnant woman based on its mechanism of action.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions)
It is not known whether sacituzumab govitecan or SN-38 is distributed into human milk.1 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.1 The effects of the drug on breast-fed infants or on the production of milk are unknown.1
Safety and efficacy of sacituzumab govitecan-hziy have not been established in pediatric patients.1
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.1 No overall differences in safety and efficacy were observed between geriatric patients and younger adults.1
Age does not appear to affect the pharmacokinetics of sacituzumab govitecan.1
Exposure to sacituzumab govitecan was similar in patients with mild hepatic impairment (serum bilirubin concentration not exceeding the ULN and AST concentration exceeding the ULN, or serum bilirubin concentration exceeding the ULN, but no more than 1.5 times the ULN with any AST concentration) and those with normal hepatic function.1
The pharmacokinetics of sacituzumab govitecan have not been established in patients with moderate or severe hepatic impairment (serum bilirubin concentration exceeding 1.5 times the ULN, or AST and ALT concentration exceeding 3 times the ULN); however, systemic exposure to SN-38 may be elevated in such patients due to decreased hepatic UGT1A1 activity.1
The pharmacokinetics of sacituzumab govitecan have not been established in patients with renal impairment or end-stage renal disease (creatinine clearance of 30 mL/minute or less); however, renal elimination of SN-38 is minimal.1
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.1, 6, 14
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.1, 14
Drugs Affecting Uridine Diphosphate-glucuronosyltransferase (UGT)
Concomitant use of sacituzumab govitecan with inhibitors of UGT1A1 may result in increased systemic exposure to SN-38 and an increased risk of adverse reactions.1, 14 Concomitant use of sacituzumab govitecan with UGT1A1 inhibitors should be avoided.1, 14
Concomitant use of sacituzumab govitecan with inducers of UGT1A1 may result in substantially decreased systemic exposure to SN-38.1, 14 Concomitant use of sacituzumab govitecan with UGT1A1 inducers should be avoided.1, 14
Sacituzumab govitecan, a trophoblast antigen-2 (Trop-2)-directed antibody-drug conjugate, is an antineoplastic agent.1, 2, 4, 5, 6, 12, 14 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.5, 14 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).2, 5, 12, 14 Following binding of the antibody to Trop-2-expressing cancer cells, the resultant complex is internalized by the cell.1 SN-38 is released via hydrolysis of the maleimide-containing crosslinker CL2A and also may be released extracellularly into the tumor microenvironment.1, 2, 8, 12 SN-38 interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single-strand breaks. 1, 2, 14 The resulting DNA damage leads to apoptosis and cell death.1, 2, 14
Sacituzumab govitecan has a high drug-to-antibody ratio (approximately 7-8 molecules of SN-38 are attached to each antibody molecule).1, 2, 5, 12 Sacituzumab govitecan releases more than 90% of SN-38 over approximately 3 days. 6, 12 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.1, 6, 12 SN-38 is metabolized by UGT1A1 to the glucuronide metabolite SN-38G.1 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.12 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.6, 12 The terminal half-lives of the antibody-drug conjugate and free SN-38 are 16 and 18 hours, respectively.1
Population pharmacokinetic analyses indicate that age and race do not appear to have clinically important effects on the pharmacokinetics of the antibody-drug conjugate.1
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion only | 180 mg | Immunomedics |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions July 26, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Immunomedics. Trodelvy® (sacituzumab govitecan-hziy) for injection, for intravenous use prescribing information. Morris Plains, NJ; 2020 Apr.
2. Goldenberg DM, Sharkey RM. Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy. Expert Opin Biol Ther . 2020; 20:871-885. [PubMed 32301634]
3. Bardia A, Mayer IA, Diamond JR et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol . 2017; 35:2141-2148. [PubMedCentral][PubMed 28291390]
4. Bardia A, Mayer IA, Vahdat LT et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med . 2019; 380:741-751. [PubMed 30786188]
5. Bardia A. A closer look at sacituzumab govitecan-hziy. Clin Adv Hematol Oncol . 2020; 18:715-717. [PubMed 33406063]
6. Seligson JM, Patron AM, Berger MJ et al. Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Ann Pharmacother . 2021; 55:921-931. [PubMed 33070624]
8. Food and Drug Administration,.Center for Drug Evaluation and Research. Application number 761115Orig1s000: Multi-discipline review. From FDA website [Web]
9. Bardia A, Tolaney SM, Loirat D et al. ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treament of physician's choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). European Society for Medical Oncology Virtual Congress. Abstract No. LBA17.
10. Immunomedics. Trodelvy® Reconstitution and Administation Guide. From the Trodelvy® website. Accessed 2021 Mar 28. [Web]
11. Schwartzberg LS, Navari RM. Safety of Polysorbate 80 in the Oncology Setting. Adv Ther . 2018; 35:754-767. [PubMedCentral][PubMed 29796927]
12. Ocean AJ, Starodub AN, Bardia A et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer . 2017; 123:3843-3854. [PubMed 28558150]
14. Wahby S, Fashoyin-Aje L, Osgood CL et al. FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Clin Cancer Res . 2021; 27:1850-1854. [PubMed 33168656]
15. Lv X, Xia Y, Finel M et al. Recent progress and challenges in screening and characterization of UGT1A1 inhibitors. Acta Pharm Sin B . 2019; 9:258-278. [PubMedCentral][PubMed 30972276]