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Sacituzumab Govitecan-hziy

Class: Antineoplastic Agents
Brands: Trodelvy

Medically reviewed by Drugs.com on May 11, 2020. Written by ASHP.

Warning

WARNING: NEUTROPENIA AND DIARRHEA

  • Severe neutropenia may occur. Withhold sacituzumab govitecan-hziy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.

  • Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold sacituzumab govitecan-hziy until resolved to ≤ Grade 1 and reduce subsequent doses.

Introduction

Sacituzumab govitecan-hziy is an antineoplastic agent.

Uses for Sacituzumab Govitecan-hziy

Sacituzumab govitecan-hziy has the following uses:

Sacituzumab govitecan-hziy is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Sacituzumab Govitecan-hziy Dosage and Administration

General

Sacituzumab govitecan-hziy is available in the following dosage form(s) and strength(s):

For injection: 180 mg lyophilized powder in single-dose vials for reconstitution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration
  • Do NOT substitute sacituzumab govitecan-hziy for or use with other drugs containing irinotecan or its active metabolite SN-38.

  • For intravenous infusion only. Do not administer as an intravenous push or bolus.

  • The recommended dose is 10 mg/kg once weekly on Days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity.

  • Premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting is recommended.

  • Monitor patients during the infusion and for at least 30 minutes after completion of infusion. Treatment interruption and/or dose reduction may be needed to manage adverse reactions.

  • See Full Prescribing Information for preparation and administration instructions.

Cautions for Sacituzumab Govitecan-hziy

Contraindications

Severe hypersensitivity reaction to sacituzumab govitecan-hziy.

Warnings/Precautions

Neutropenia

Sacituzumab govitecan-hziy can cause severe or life-threatening neutropenia. Withhold sacituzumab govitecan-hziy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold sacituzumab govitecan-hziy for neutropenic fever. Dose modifications may be required due to neutropenia.

Febrile neutropenia occurred in 6% (24/408) patients treated with sacituzumab govitecan-hziy, including 8% (9/108) patients with mTNBC after at least two prior therapies. Less than 1% (1/408) of patients had febrile neutropenia leading to permanent discontinuation.

The incidence of Grade 1-4 neutropenia was 64% in patients with mTNBC (n=108). In all patients treated with sacituzumab govitecan-hziy (n=408), the incidence of Grade 1-4 neutropenia was 54%; Grade 4 neutropenia occurred in 13%. Less than 1% (2/408) of patients permanently discontinued treatment due to neutropenia.

Diarrhea

Sacituzumab govitecan-hziy can cause severe diarrhea. Withhold sacituzumab govitecan-hziy for Grade 3-4 diarrhea at the time of scheduled treatment administration and resume when resolved to ≤ Grade 1.

At the onset of diarrhea, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated.

Patients who exhibit an excessive cholinergic response to treatment with sacituzumab govitecan-hziy (e.g., abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Diarrhea occurred in 63% (68/108) of patients with mTNBC and 62% (254/408) of all patients treated with sacituzumab govitecan-hziy. In each population, events of Grade 3-4 occurred in 9% (10/108) of mTNBC patients and 9% (36/408) of all patients treated with sacituzumab govitecan-hziy. Four out of 408 patients (<1%) discontinued treatment because of diarrhea. Neutropenic colitis was observed in 2% (2/108) of patients in the mTNBC cohort and 1% of all patients treated with sacituzumab govitecan-hziy.

Hypersensitivity

Sacituzumab govitecan-hziy can cause severe and life-threatening hypersensitivity. Anaphylactic reactions have been observed in clinical trials with sacituzumab govitecan-hziy.

Hypersensitivity reactions within 24 hours of dosing occurred in 37% (151/408) of patient treated with sacituzumab govitecan-hziy. Grade 3-4 hypersensitivity occurred in 1% (6/408) of patients treated with sacituzumab govitecan-hziy. The incidence of hypersensitivity reactions leading to permanent discontinuation of sacituzumab govitecan-hziy was 1% (3/408).

Pre-infusion medication for patients receiving sacituzumab govitecan-hziy is recommended. Observe patients closely for infusion-related reactions during each sacituzumab govitecan-hziy infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.

Nausea and Vomiting

Sacituzumab govitecan-hziy is emetogenic. Nausea occurred in 69% (74/108) of patients with mTNBC and 69% (281/408) of all patients treated with sacituzumab govitecan-hziy. Grade 3 nausea occurred in 6% (7/108) and 5% (22/408) of these populations, respectively.

Vomiting occurred in 49% (53/108) of patients with mTNBC and 45% (183/408) of all patients treated with sacituzumab govitecan-hziy. Grade 3 vomiting occurred in 6% (7/108) and 4% (16/408) of these patients, respectively.

Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV).

Withhold sacituzumab govitecan-hziy doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to ≤ Grade 1.

Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Use in Patients with Reduced UGT1A1 Activity

Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia and may be at increased risk for other adverse reactions following initiation of sacituzumab govitecan-hziy treatment.

In 84% (343/408) of patients who received sacituzumab govitecan-hziy (up to 10 mg/kg on Days 1 and 8 of a 21-day cycle) and had retrospective UGT1A1 genotype results available, the incidence of Grade 4 neutropenia was 26% (10/39) in patients homozygous for the UGT1A1*28 allele, 13% (20/155) in patients heterozygous for the UGT1A1*28 allele and 11% (16/149) in patients homozygous for the wild-type allele.

Closely monitor patients with reduced UGT1A1 activity for severe neutropenia. The appropriate dose for patients who are homozygous for UGT1A1*28 is not known and should be considered based on individual patient tolerance to treatment.

Embryo-fetal Toxicity

Based on its mechanism of action, sacituzumab govitecan-hziy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Sacituzumab govitecan-hziy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with sacituzumab govitecan-hziy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with sacituzumab govitecan-hziy and for 3 months after the last dose.

Specific Populations

Pregnancy

Risk Summary: Based on its mechanism of action, sacituzumab govitecan-hziy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Sacituzumab govitecan-hziy contains a genotoxic component, SN-38, and is toxic to rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively.

Animal Data: There were no reproductive and developmental toxicology studies conducted with sacituzumab govitecan-hziy.

Lactation

Risk Summary: There is no information regarding the presence of sacituzumab govitecan-hziy or SN-38 in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 1 month after the last dose of sacituzumab govitecan-hziy.

Females and Males of Reproductive Potential

Verify the pregnancy status of females of reproductive potential prior to the initiation of sacituzumab govitecan-hziy.

Sacituzumab govitecan-hziy can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with sacituzumab govitecan-hziy and for 6 months after the last dose.

Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with sacituzumab govitecan-hziy and for 3 months after the last dose.

Based on findings in animals, sacituzumab govitecan-hziy may impair fertility in females of reproductive potential.

Pediatric Use

Safety and effectiveness of sacituzumab govitecan-hziy have not been established in pediatric patients.

Geriatric Use

Of the patients who received sacituzumab govitecan-hziy, 19/108 (18%) patients with mTNBC and 144/408 (35%) of all patients were ≥ 65 years old. No overall differences in safety and effectiveness were observed between these patients and younger patients.

Hepatic Impairment

No adjustment to the starting dose is required when administering sacituzumab govitecan-hziy to patients with mild hepatic impairment (bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) and AST/ALT < 3 times the ULN).

The exposure of sacituzumab govitecan-hziy in patients with mild hepatic impairment (bilirubin less than or equal to ULN and AST greater than ULN, or bilirubin greater than 1 to 1.5 times the ULN and AST of any level; n=12) was similar to patients with normal hepatic function (bilirubin or AST less than ULN; n=45).

The safety of sacituzumab govitecan-hziy in patients with moderate or severe hepatic impairment has not been established. Sacituzumab govitecan-hziy has not been tested in patients with serum bilirubin > 1.5 times the ULN, or AST and ALT > 3 times the ULN, or AST and ALT > 5 times the ULN and associated with liver metastases.

No dedicated trial was performed to investigate the tolerability of sacituzumab govitecan-hziy in patients with moderate or severe hepatic impairment. No recommendations can be made for the starting dose in these patients.

Common Adverse Effects

Most common adverse reactions (incidence ≥25%) in patients with mTNBC are nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • UGT1A1 inhibitors or inducers: Avoid concomitant use.

Actions

Mechanism of Action

Sacituzumab govitecan-hziy is a Trop-2-directed antibody-drug conjugate. Sacituzumab is a humanized antibody that recognizes Trop-2. The small molecule, SN-38, is a topoisomerase I inhibitor, which is covalently attached to the antibody by a linker. Pharmacology data suggest that sacituzumab govitecan-hziy binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38 via hydrolysis of the linker. 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-hziy decreased tumor growth in mouse xenograft models of triple-negative breast cancer.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling.

Neutropenia

Advise patients of the risk of neutropenia. Instruct patients to immediately contact their healthcare provider if they experience fever, chills, or other signs of infection.

Diarrhea

Advise patients of the risk of diarrhea. Instruct patients to immediately contact their healthcare provider if they experience diarrhea for the first time during treatment; black or bloody stools; symptoms of dehydration such as lightheadedness, dizziness, or faintness; inability to take fluids by mouth due to nausea or vomiting; or inability to get diarrhea under control within 24 hours.

Hypersensitivity

Inform patients of the risk of serious infusion reactions and anaphylaxis. Instruct patients to immediately contact their healthcare provider if they experience facial, lip, tongue, or throat swelling, urticaria, difficulty breathing, lightheadedness, dizziness, chills, rigors, wheezing, pruritus, flushing, rash, hypotension or fever, that occur during or within 24 hours following the infusion.

Nausea/Vomiting

Advise patients of the risk of nausea and vomiting. Premedication according to established guidelines with a two or three drug regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) is also recommended. Additional antiemetics, sedatives, and other supportive measures may also be employed as clinically indicated. All patients should receive take-home medications for preventing and treating delayed nausea and vomiting, with clear instructions. Instruct patients to immediately contact their healthcare provider if they experience uncontrolled nausea or vomiting.

Embryo-fetal Toxicity

Advise female patients to contact their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of the pregnancy.

Contraception

Advise female patients of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of sacituzumab govitecan-hziy.

Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of sacituzumab govitecan-hziy.

Lactation

Advise women not to breastfeed during treatment and for 1 month after the last dose of sacituzumab govitecan-hziy.

Infertility

Advise females of reproductive potential that sacituzumab govitecan-hziy may impair fertility.

Additional Information

AHFSfirstRelease. For additional information 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 uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

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.

Sacituzumab Govitecan-hziy

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion only

180 mg

Trodelvy

Immunomedics Inc.

AHFS Drug Information. © Copyright 2021, Selected Revisions May 11, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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