Dosing & Adverse Reaction Management Strategies | TRODELVY® (sacituzumab govitecan- hziy) | Official HCP Site

TRODELVY® (sacituzumab govitecan-hziy) 180 mg for injection logo

Start TRODELVY at 10 mg/kg

The recommended dosage of TRODELVY is 10 mg/kg intravenously on Days 1 and 8 of 21-day continuous treatment cycles1

  • Continue treatment until disease progression or unacceptable toxicity
  • Do not administer TRODELVY at doses greater than 10 mg/kg
  • Administer TRODELVY as an intravenous infusion only. Do not administer as an intravenous push or bolus
  • Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite, SN-38

21-day treatment cycles1

10 mg/kg 10 mg/kg Continue treatment until disease progression or unacceptable toxicity

First infusion1

  • Administer infusion over 3 hours
  • Observe patients during the infusion and for at least 30 minutes following the initial dose for signs or symptoms of infusion-related reactions

Subsequent infusions1

  • Administer infusion over 1 to 2 hours if prior infusions were tolerated
  • Observe patients during the infusion and for at least 30 minutes after the infusion

Premedication recommended prior to each dose of TRODELVY for the following1:

To prevent chemotherapy-induced nausea and vomiting (CINV), premedicate with:

  • Dexamethasone AND
  • 5-HT3 receptor antagonist OR NK1 receptor antagonist
  • Other drugs as indicated

To prevent infusion reactions, premedicate with:

  • Antipyretics
  • H1 and H2 blockers
  • Corticosteroids (for patients with a prior infusion reaction)

In patients with a prior excessive cholinergic reaction,* premedicate with:

  • Atropine or other appropriate premedication

Medications and emergency equipment to treat infusion-related reactions including anaphylaxis should be available for immediate use.1

*Eg, abdominal cramping, diarrhea, salivation, etc.1

Management strategies for ARs through dose modifications

Consider G-CSF as clinically indicated

  • Withhold or discontinue TRODELVY to manage adverse reactions as described above. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made
  • Slow or interrupt the infusion rate of TRODELVY if the patient develops an infusion-related reaction. Permanently discontinue TRODELVY for life-threatening infusion-related reactions
SEVERE NEUTROPENIA
Adverse reaction

Grade 4 neutropenia ≥7 days
OR
Grade 3–4 febrile neutropenia
OR
At time of scheduled treatment, Grade
3-4 neutropenia, which delays dosing by
2 or 3 weeks for recovery to ≤Grade 1

Occurrence Dose modification
First 25% dose reduction and administer G-CSF
Second 50% dose reduction and administer G-CSF
Third Discontinue treatment and administer G-CSF
Adverse reaction

At time of scheduled treatment, Grade 3–4 neutropenia which delays dosing beyond 3 weeks for recovery to ≤Grade 1
Occurrence Dose modification
First Discontinue treatment and administer G-CSF
SEVERE NON-NEUTROPENIC TOXICITY
Adverse reaction

Grade 4 non-hematologic toxicity of any duration
OR
Any Grade 3–4 nausea, vomiting or diarrhea due to treatment that is not controlled with antiemetics and anti-diarrheal agents
OR
Other Grade 3–4 non-hematologic toxicity persisting >48 hours despite optimal medical management
OR
At time of scheduled treatment, Grade 3–4 non-neutropenic hematologic or non-hematologic toxicity, which delays dose by 2 or 3 weeks for recovery to ≤Grade 1

Occurrence Dose modification
First 25% dose reduction
Second 50% dose reduction
Third Discontinue treatment
Adverse reaction

In the event of Grade 3–4 non-neutropenic hematologic or non-hematologic toxicity, which does not recover to ≤Grade 1 within 3 weeks
Occurrence Dose modification
First Discontinue treatment
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If patients experience neutropenia, be ready with G-CSF prophylaxis or support to help patients stay on therapy if clinically indicated/appropriate1

Reference: 1. TRODELVY. Prescribing information. Gilead Sciences, Inc.; November 2024.

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G-CSF=granulocyte-colony stimulating factor; NK1=neurokinin 1.

INDICATIONS

TRODELVY® (sacituzumab govitecan-hziy) 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 them for metastatic disease.
  • Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: NEUTROPENIA AND DIARRHEA
  • Severe or life-threatening neutropenia may occur. Withhold TRODELVY 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. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS
  • Severe hypersensitivity reaction to TRODELVY.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold TRODELVY 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 TRODELVY for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, 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 can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with TRODELVY. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting 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.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based 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 reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY 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 TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

Please see full Prescribing Information, including BOXED WARNING.