Intravenous Unresectable locally advanced triple-negative breast cancer, Unresectable metastatic triple-negative breast cancer
Adult: For patients who have received ≥2 prior systemic therapies, at least 1 of them given for unresectable locally advanced or metastatic disease: 10 mg/kg once weekly via infusion on Days 1 and 8 of a 21-day treatment cycle. Administer the 1st infusion over 3 hours; if well-tolerated, subsequent infusions may be given over 1-2 hours. Continue until disease progression or unacceptable toxicity. Premedicate with antipyretics, antihistamines, and antiemetics prior to infusion; corticosteroids may also be considered for patients who had previous infusion-related reactions. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability. Recommended therapeutic indications may vary between countries (refer to local detailed product guidelines).
Intravenous Locally advanced urothelial cancer, Metastatic urothelial cancer
Adult: For patients who have previously received platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor: 10 mg/kg once weekly via infusion on Days 1 and 8 of a 21-day treatment cycle. Administer the 1st infusion over 3 hours; if well-tolerated, subsequent infusions may be given over 1-2 hours. Continue until disease progression or unacceptable toxicity. Premedicate with antipyretics, antihistamines, and antiemetics prior to infusion; corticosteroids may also be considered for patients who had previous infusion-related reactions. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability. Recommended therapeutic indications may vary between countries (refer to local detailed product guidelines).
Special Patient Group
Pharmacogenomics:
SN-38, the small molecule moiety of sacituzumab govitecan, is metabolised by the UGT1A1 enzyme. Genetic variants of the UGT1A1 gene such as the UGT1A1*28 allele may result in reduced UGT1A1 enzyme activity. The prevalence of individuals with homozygous UGT1A1*28 allele is approx 20% in the Black or African American population, 10% in the White population, and 2% in the East Asian descent. Decreased function alleles other than UGT1A1*28 may be present in certain populations.
Patients who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, anaemia, and other adverse reactions due to the reduced glucuronidation of SN-38. Closely monitor individuals with known reduced UGT1A1 activity for adverse reactions, especially severe neutropenia. Withhold or permanently discontinue treatment depending on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions (which may indicate decreased UGT1A1 activity).
Hepatic Impairment
Moderate to severe: Not recommended.
Reconstitution
Allow the required number of vials based on the calculated dose to warm to room temperature. Slowly reconstitute each 180 mg vial with 20 mL of NaCl 0.9% inj to make a concentration of 10 mg/mL. Swirl the vials gently and allow to dissolve for up to 15 minutes; do not shake. To prepare the diluted solution for infusion, calculate the required amount of the reconstituted solution and determine the final volume of infusion solution to deliver a concentration of 1.1-3.4 mg/mL (total volume per infusion bag must not exceed 500 mL). Withdraw and discard the volume of NaCl 0.9% inj from the infusion bag necessary to achieve the appropriate concentration for infusion, then slowly add the calculated amount of reconstituted solution into the infusion bag. Do not shake.
Contraindications
Hypersensitivity to sacituzumab govitecan or to previous irinotecan therapy. Pregnancy and lactation.
Special Precautions
Patients with known reduced UGT1A1 activity, particularly those who are homozygous for UGT1A1*28 allele. Do not substitute sacituzumab govitecan for (or use with) other agents containing irinotecan or its active metabolite, SN-38. Moderate to severe hepatic impairment.
Adverse Reactions
Significant: Bone marrow suppression (e.g. anaemia, febrile neutropenia, leucopenia, thrombocytopenia, lymphopenia); nausea, vomiting, severe diarrhoea. Rarely, neutropenic enterocolitis. Gastrointestinal disorders: Abdominal pain or distension, constipation, dysgeusia, stomatitis. General disorders and administration site conditions: Fatigue, pyrexia, oedema. Investigations: Increased weight, decreased serum albumin; increased AST, ALT, and serum alkaline phosphatase. Metabolism and nutrition disorders: Decreased appetite, hypokalaemia, hypomagnesaemia, hypophosphataemia, hypocalcaemia, hyperglycaemia, dehydration. Musculoskeletal and connective tissue disorders: Arthralgia, back pain, pain in the extremity. Nervous system disorders: Headache, dizziness, neuropathy. Psychiatric disorders: Insomnia. Renal and urinary disorders: UTI, acute kidney injury, haematuria. Respiratory, thoracic and mediastinal disorders: URTI, bronchitis, pneumonia, cough, dyspnoea, epistaxis. Skin and subcutaneous tissue disorders: Alopecia, rash, pruritus, dry skin. Potentially Fatal: Hypersensitivity reactions, including severe anaphylactic reactions; severe neutropenia.
IV: Z (Based on mechanism of action, may cause teratogenicity and embryo-foetal lethality. Avoid during pregnancy.)
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery. Women of childbearing potential must use proven birth control methods during therapy and for 6 months after stopping the treatment. Male patients with female partners of childbearing potential must use reliable birth control methods during treatment and for 3 months after the last dose. Discontinue breastfeeding during therapy and for 1 month following the last dose.
Monitoring Parameters
Verify the pregnancy status prior to treatment initiation in females of childbearing potential. Obtain complete blood count, prothrombin time, partial thromboplastin time and complete metabolic panel prior to each dose and as clinically indicated. Closely monitor for signs of infusion-related reactions during and for at least 30 minutes after the infusion. Assess for signs of hypersensitivity reactions, neutropenic fever, diarrhoea, nausea, and vomiting.
Drug Interactions
May increase the incidence of adverse reactions with UGT1A1 inhibitors (e.g. ketoconazole, propofol) due to a potential increase in systemic exposure to SN-38. Exposure to SN-38 may be substantially reduced when given to patients concomitantly receiving UGT1A1 inducers (e.g. rifampicin, carbamazepine, phenytoin, protease inhibitors).
Action
Description: Mechanism of Action: Sacituzumab govitecan is a trophoblast antigen-2 (Trop-2)-directed antibody-drug conjugate composed of sacituzumab (a humanised immunoglobulin G1 [IgG1] kappa monoclonal antibody) covalently linked to SN-38 (a topoisomerase I inhibitor) via a hydrolysable linker. It binds to Trop-2-expressing cancer cells and is internalised, subsequently releasing the SN-38 via hydrolysis of the linker. SN-38 interacts with topoisomerase I and inhibits the re-ligation of topoisomerase I-induced single-strand breaks, leading to DNA damage, apoptosis and cell death. Pharmacokinetics: Distribution: Volume of distribution: 2.96 L (sacituzumab govitecan). Metabolism: SN-38, the small molecule moiety of sacituzumab govitecan, is mainly metabolised by UGT1A1. Excretion: Elimination half-life: 15.3 hours (sacituzumab govitecan); 19.7 hours (free SN-38).
Chemical Structure
Sacituzumab govitecan Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 91668186, Sacituzumab govitecan. https://pubchem.ncbi.nlm.nih.gov/compound/Sacituzumab-govitecan. Accessed May 30, 2023.
Storage
Intact vial: Store between 2-8°C. Diluted solution for infusion: Store between 2-8°C for up to 24 hours. Do not freeze. Protect intact vial and infusion bag from light (including during infusion). Following refrigeration, administer the diluted solution at room temperature up to 25°C within 8 hours (including infusion time). This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01FX17 - sacituzumab govitecan ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.
References
Annotation of EMA Label for Sacituzumab Govitecan-hziy and UGT1A1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 11/01/2023.Annotation of FDA Label for Sacituzumab Govitecan-hziy and UGT1A1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 11/01/2023.Anon. Sacituzumab Govitecan-hziy. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 10/01/2023.Anon. Sacituzumab Govitecan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/01/2023.Anon. UGT1A1 - Sacituzumab Govitecan (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/01/2023.Buckingham R (ed). Sacituzumab Govitecan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/01/2023.Joint Formulary Committee. Sacituzumab Govitecan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/01/2023.Trodelvy 180 mg Powder for Concentrate for Solution for Infusion (Gilead Sciences Ltd). MHRA. https://products.mhra.gov.uk. Accessed 10/01/2023.Trodelvy Powder, for Solution (Gilead Sciences). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/01/2023.
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