Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
sacituzumab govitecan
Sacituzumab govitecan is a Trop-2-directed antibody-drug conjugate (ADC). It is composed of a humanized antibody (sacituzumab) that is covalently attached by a linker (CL2A) to SN-38, a topoisomerase I inhibitor and an active metabolite of irinotecan. After binding to Trop-2-expressing cancer cells, the ADC is internalized. SN-38 is subsequently released via hydrolysis of the linker, leading to DNA damage, apoptosis, and cell death.
No metabolism studies with sacituzumab govitecan have been conducted. The antibody moiety is expected to be catabolized to amino acids. SN-38 is metabolized via UGT1A1.
| Inactive metabolites | Yes |
| Half-life | 15 hours (sacituzumab govitecan); 20 hours (SN-38) |
| Feces | Major route (for SN-38; based on irinotecan elimination) |
- Breast cancer
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
Extravasation Potential: None
The following adverse events were reported in > 5% of patients treated with sacituzumab govitecan in a Phase 3 study of patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who received at least two prior treatments. Other severe or life-threatening adverse effects may also be included.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | QT interval prolonged (5%) | E | |||
| Dermatological | Alopecia (47%) | D L | |||
| Rash (12%) | E | ||||
| Gastrointestinal | Abdominal pain (21%) | E | |||
| Anorexia, weight loss (28%) | E | ||||
| Constipation (37%) | E | ||||
| Diarrhea (65%) (11% severe) | I E | ||||
| Mucositis (10%) | E | ||||
| Nausea, vomiting (62%) (3% severe) | I E | ||||
| General | Edema - limbs (9%) | E | |||
| Fatigue (52%) (4% severe) | E | ||||
| Hematological | Myelosuppression ± infection, bleeding (64%) (52% severe) | E | |||
| Hepatobiliary | ↑ LFTs (11%) | E | |||
| Hypersensitivity | Hypersensitivity (34%) (1% severe) | I E | |||
| Infusion related reaction (<1%) | I | ||||
| Metabolic / Endocrine | Abnormal electrolyte(s) (16%) (↓ K, ↓ Mg, ↓ PO4, ↓ Ca, ↓ Na) | E | |||
| Hyperglycemia (7%) | E | ||||
| Musculoskeletal | Musculoskeletal pain (16%) | E | |||
| Nervous System | Dizziness (10%) | E | |||
| Dysgeusia (9%) | E | ||||
| Headache (18%) | I E | ||||
| Insomnia (11%) | E | ||||
| Respiratory | Cough, dyspnea (24%) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for sacituzumab govitecan include diarrhea, myelosuppression ± infection, nausea, vomiting, fatigue, alopecia, constipation, hypersensitivity, anorexia, weight loss, cough, dyspnea and abdominal pain.
Diarrhea may be severe with sacituzumab govitecan. This may be due to either early cholinergic syndrome or delayed SN-38-related diarrhea. Patients should be monitored, provided with fluid and electrolytes as required, and evaluated for infectious causes at the onset. If diarrhea is non-infectious, loperamide 4 mg should be initiated, followed by 2 mg with every episode of diarrhea (up to a maximum of 16 mg daily). Discontinue loperamide 12 hours after diarrhea resolves. Similar to irinotecan, patients with severe cholinergic symptoms (e.g. abdominal cramping, salivation, diarrhea) should receive appropriate premedication (e.g. atropine) for subsequent treatments.
Severe neutropenia, including fatal events, has been reported with sacituzumab govitecan. Grade 3-4 neutropenia occurred commonly in clinical trials (51% of patients); febrile neutropenia was reported in 6% of patients. Dose interruption and/or appropriate management including initiation of supportive treatment (e.g. G-CSF, anti-infectives) may be required (see Dosing section). Patients with known reduced UGT1A1 activity (e.g. Gilbert's syndrome or homozygous for the UGT1A1*28 allele) may have an increased risk for neutropenia, febrile neutropenia, anemia, or other adverse effects and should be closely monitored. Acute early-onset or unusually severe adverse reactions may indicate reduced UGT1A1 enzyme activity.
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Patients with known reduced UGT1A1 activity (e.g. Gilbert's syndrome or homozygous for the UGT1A1*28 allele) may have an increased risk for neutropenia, febrile neutropenia, anemia, or other adverse effects and should be closely monitored. Acute early-onset or unusually severe adverse reactions may indicate reduced UGT1A1 enzyme activity. Hold or discontinue sacituzumab govitecan as clinically indicated.
Do NOT substitute sacituzumab govitecan for or use with other drugs containing irinotecan or its active metabolite, SN-38.
Pre-medications:
- Prophylaxis for infusion reaction
- Administer antipyretics, H1 and H2 blockers prior to infusion.
- Administer antipyretics, H1 and H2 blockers prior to infusion.
- Prophylaxis for cholinergic response
- Patients with excessive cholinergic response (e.g., abdominal cramping, diarrhea, salivation) can receive appropriate premedication (e.g., atropine) for subsequent treatments.
- Patients with excessive cholinergic response (e.g., abdominal cramping, diarrhea, salivation) can receive appropriate premedication (e.g., atropine) for subsequent treatments.
Other Supportive Care:
- For non-infectious diarrhea, promptly initiate loperamide 4 mg, followed by 2 mg with every episode of diarrhea (up to a maximum of 16 mg daily). Discontinue loperamide 12 hours after diarrhea resolves.
| Dose Level | Sacituzumab Dose (mg/kg) |
| 0 | 10 |
| -1 | 7.5 |
| -2 | 5 |
| -3 | Discontinue |
Hematologic Toxicity:
| Toxicity | Action |
| Grade 3 neutropenia | Hold* until resolved. If treatment delayed by 1 week, resume at same dose, consider G-CSF support. If treatment delayed by 2-3 weeks, resume at 1 dose level ↓ and administer G-CSF. Discontinue if 3rd occurrence. |
| Grade 4 neutropenia | Hold* until resolved. If lasts > 7 days or treatment delayed by 2-3 weeks, resume at 1 dose level ↓ and administer G-CSF. Discontinue if 3rd occurrence. |
| Febrile neutropenia | Hold* until resolved. Resume at 1 dose level ↓ and administer G-CSF. Discontinue if 3rd occurrence. |
| Other Grade 3 or 4 hematologic toxicity (e.g., anemia and thrombocytopenia) | Hold* until resolved. If treatment delayed by 2-3 weeks, resume at 1 dose level ↓. Discontinue if 3rd occurrence. |
*On day 1, do not resume until ANC ≥ 1.5 x 109/L, Platelets ≥ 75 x 109/L, Hgb ≥ 100 g/L, and non-hematologic toxicities recover to ≤ Grade 1.
On day 8, do not resume until ANC ≥ 1 x 109/L, Platelets ≥ 75 x 109/L, Hgb ≥ 100 g/L, and non-hematologic toxicities recover to ≤ Grade 1.
Discontinue sacituzumab govitecan if dose is held for > 3 weeks.
Non-hematologic Toxicity:
| Toxicity | Action |
| Grade 3 or 4 nausea / vomiting / diarrhea** | Hold* until resolved. Resume at 1 dose level ↓. Discontinue if 3rd occurrence. |
Other Grade 3 non-hematologic toxicity (persisting > 48h despite medical management or requiring dose hold for 2-3 weeks) Other Grade 4 non-hematologic toxicity | Hold* until resolved. Resume at 1 dose level ↓. Discontinue if 3rd occurrence. |
*On day 1, do not resume until ANC ≥ 1.5 x 109/L, Platelets ≥ 75 x 109/L, Hgb ≥ 100 g/L, and non-hematologic toxicities recover to ≤ Grade 1.
On day 8, do not resume until ANC ≥ 1 x 109/L, Platelets ≥ 75 x 109/L, Hgb ≥ 100 g/L, and non-hematologic toxicities recover to ≤ Grade 1.
Discontinue sacituzumab govitecan if dose is held for > 3 weeks.
**Not controlled with supportive care (antiemetics or anti-diarrheals).
Management of Infusion-related reactions
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
|
|
| 3 or 4 |
|
|
Sacituzumab govitecan exposure in patients with mild hepatic impairment is similar to patients with normal hepatic function.
| Bilirubin | AST | Sacituzumab Dose | |
| < ULN | and | > ULN | No dose adjustment required. |
| >1 to 1.5 x ULN | and | Any | |
| >1.5 to 3.0 × ULN | and | Any | Not studied. |
| > 3 x ULN | and | Any | Avoid; not studied. |
Renal elimination contributes minimally to the excretion of SN-38. There are no data on the use of sacituzumab govitecan in patients with severe renal impairment (CrCl 15-29 mL/min), or end-stage renal disease (CrCl < 15 mL/min).
No dose adjustment is required in patients > 65 years.
Safety and efficacy were similar between patients > 65 years and younger patients with mTNBC.
In patients with HR-positive/HER2-negative breast cancer, there were higher rates of serious adverse reactions and discontinuation in patients > 65 years compared to younger patients.
Do NOT substitute sacituzumab govitecan for or use with other drugs containing irinotecan or its active metabolite, SN-38.
- After reconstitution, dilute in an infusion bag with NS to a concentration of 1.1 to 3.4 mg/mL.
- The infusion bag must be made of polyvinyl chloride, polyolefin (polypropylene and/or polyethylene) or ethylene vinyl acetate to minimize foaming.
- Do not shake. Protect the infusion bag from light.
- Administer as an IV infusion only. Do NOT administer as an IV push or bolus.
- Infuse over 3 hours for the first infusion. If well tolerated, infuse over 1-2 hours for subsequent infusions.
- Observe patients during and for at least 30 minutes after each infusion.
- Do not mix or infuse with other agents.
- Flush IV line with 20 mL of NS at the end of infusion.
- Store unopened vials between 2°C to 8°C in the original carton. Protect from light. Do not freeze.
- Patients who are hypersensitive to this drug or any of its components
Other Drug Properties:
- Carcinogenicity: Unknown
Pregnancy and Lactation:
- Mutagenicity: Unknown
- Clastogenicity: Yes
- Genotoxicity: Yes
- Embryotoxicity: Probable
- Teratogenicity: Probable
Sacituzumab govitecan is not recommended for use in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for at least 6 months after the last dose.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for at least 3 months after the last dose.
- Excretion into breast milk: Unknown
Breastfeeding is not recommended during treatment and for 1 month after the last dose.
- Fertility effects: Probable
Female fertility may be affected.
No formal drug interaction studies were conducted with sacituzumab govitecan.
SN-38 (the small molecule moiety of sacituzumab govitecan) is primarily metabolized via UGT1A1. Inhibitors or inducers of CYP3A are not anticipated to impact SN-38 exposure.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| UGT1A1 inhibitors (e.g., propofol, ketoconazole, EGFR tyrosine kinase inhibitors) | ↑ SN-38 toxicity (theoretical) | ↓ metabolism of SN-38 | Caution |
| UGT1A1 inducers (e.g., carbamazepine, phenytoin, rifampicin, protease inhibitors) | ↓ SN-38 effect (theoretical) | ↑ metabolism of SN-38 | Caution |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Closely monitor for toxicity in patients with known reduced UGT1A1 activity, or in patients with acute early-onset or unusually severe adverse reactions that may indicate reduced UGT1A1 enzyme activity.
| Monitor Type | Monitor Frequency |
|---|---|
CBC | Baseline and before each dose |
Liver function tests | Baseline and as clinically indicated |
Renal function tests | Baseline and as clinically indicated |
Electrolytes | Baseline and as clinically indicated (especially in patients with diarrhea) |
Clinical toxicity assessment for infection, infusion reaction, diarrhea and other GI effects | At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Sacituzumab Govitecan - Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer
Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 2021;384:1529-41.
European Medicines Agency. Assessment report: Trodelvy. 14 October 2021.
eviQ Cancer Treatments Online. Clinical resource: Gilbert’s syndrome. Cancer Institute NSW. 22 Sept 2023 V.5.
Irinotecan drug monograph. Ontario Health (Cancer Care Ontario).
National Comprehensive Cancer Network. Antiemesis: NCCN Guidelines Version 1.2023.
Prescribing information: Trodelvy® (sacituzumab govitecan-hziy). Gilead Sciences, Inc. February 2023.
Product monograph: Trodelvy® (sacituzumab govitecan). Gilead Sciences Canada, Inc. July 19, 2023.
Spring LM, Nakajima E, Hutchinson J, Viscosi E, Blouin G, Weekes C, Rugo H, Moy B, Bardia A. Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. Oncologist. 2021 Oct;26(10):827-834.
Summary of Product Characteristics: Trodelvy 180 mg powder for concentrate for solution for infusion. Gilead Sciences Ltd. 1 July 2022.
December 2023 Modified Dosage with Toxicity section
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.