sacituzumab govitecan

Common name: gosartuzumab

Trade name: Trodelvy

All names: gosartuzumab, gosartuzumab lyophilized powder injection, certolizumab lyophilized powder injection, sacituzumab govitecan-hziy, Trodelvy

Indications:

TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of which is for metastatic disease.

Local advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and programmed death receptor-1 (PD-1) or programmed death ligand 1 (PDL1) inhibitors.

Dosage:

Do not use TRODELVY as a substitute for or in conjunction with other drugs containing irinotecan or its active metabolite SN-38.

For intravenous infusion only. Do not administer as an intravenous bolus.

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

Premedication is recommended to prevent infusion reactions and prevent chemotherapy-induced nausea and vomiting.

Monitor the patient during the infusion and for at least 30 minutes after the infusion is completed. Treatment interruptions and/or dose reductions may be necessary to control adverse reactions.

Specification:

200mg

Adverse reactions:

The most common adverse reactions (incidence >25%) are neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash and abdominal pain.

Contraindications:

Severe hypersensitivity reaction to TRODELVY.

Precautions:

Hypersensitivity and Infusion-Related Reactions: Hypersensitivity reactions, including severe anaphylaxis, have been observed. Monitor patients for infusion-related reactions. If a serious or life-threatening reaction occurs, permanently discontinue TRODELVY.

Nausea/Vomiting: Use antiemetic prophylaxis and discontinue TRODELVY in patients who have Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment.

Patients with reduced UGT1A1 activity: Individuals homozygous for the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1)*28 allele are at increased risk of developing neutropenia, febrile neutropenia, and anemia after initiation of TRODELVY therapy.

Embryo-Fetal Toxicity: TRODELVY may cause harm to the fetus. Advise patients of the potential risks to the fetus and to use effective contraception.

Storage:

Store vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until reconstitution. Do not freeze.

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 covalently linked to the antibody through a linker. Pharmacological data indicate that sacituzumab govitecan-hziy binds to Trop-2-expressing cancer cells and internalizes SN-38 via linker hydrolysis with subsequent release of SN-38. SN-38 interacts with topoisomerase I and prevents the religation of topoisomerase I-induced single-strand breaks. The resulting DNA damage leads to apoptosis and cell death. Sacituzumab govitecan-hziy reduces tumor growth in a mouse xenograft model of triple-negative breast cancer.

Safety and efficacy:

In a randomized clinical phase 3 trial, the research team compared the efficacy of sacituzumab-govitecan with a physician's single-agent chemotherapy regimen (eribulin, vinorelbine, capecitabine, or gemcitabine) in the treatment of patients with recurrent or refractory metastatic triple-negative breast cancer. The primary endpoint was progression-free survival in patients without brain metastases.

The research team recruited a total of 468 patients without brain metastases and randomly assigned them, of which 235 received sacituzumab-govitecan treatment and 233 received chemotherapy. The median age was 54 years; all patients had been previously treated with a taxane. Median progression-free survival was 5.6 months in the sacituzumab-govitecan group and 1.7 months in the chemotherapy group, with a hazard ratio of 0.41 for disease progression or death. The median overall survival was 12.1 months in the sacituzumab-govitecan group and 6.7 months in the chemotherapy group, with a hazard ratio of death of 0.48. The objective response rate was 35% in the sacituzumab-govitecan group and 5% in the chemotherapy group.