TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Locally Advanced or Metastatic Breast Cancer 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. ( 1.1 , 14.1 ) 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.
( 1.1 , 14.2 )
1.1Locally Advanced or Metastatic Breast Cancer
TRODELVY is 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. TRODELVY is indicated for the treatment of adult patients with 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.
Contraindications
TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY [see Warnings and Precautions (5.3) ] . Severe hypersensitivity reaction to TRODELVY. ( 4 , 5.3 )
Warnings and precautions
Hypersensitivity and Infusion-Related Reactions: Hypersensitivity reactions including severe anaphylactic reactions have been observed. Monitor patients for infusion-related reactions. Permanently discontinue TRODELVY if severe or life-threatening reactions occur. ( 5.3 ) Nausea/Vomiting: Use antiemetic preventive treatment and withhold TRODELVY for patients with Grade 3 nausea or Grade 3–4 vomiting at the time of scheduled treatment.
( 5.4 ) 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, febrile neutropenia, and anemia following initiation of TRODELVY treatment. ( 5.5 ) Embryo-Fetal Toxicity: TRODELVY can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 )
TRODELVY can cause severe, life-threatening, or fatal neutropenia as early as the first cycle of treatment. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3–4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6% of patients. The median time to first onset of neutropenia (including febrile neutropenia) was 16 days (range: 1 to 435 days). Neutropenia occurred earlier in patients with reduced UGT1A1 activity [see Warnings and Precautions (5.5) ] .
Neutropenic colitis occurred in 1.4% of patients. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm 3 on Day 1 of any cycle or below 1000/mm 3 on Day 8 of any cycle.
Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 [see Dosage and Administration (2.3) ] .
5.2Diarrhea
TRODELVY can cause severe diarrhea. Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3–4 diarrhea occurred in 11% of all patients treated with TRODELVY. 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 at the time of scheduled treatment administration and resume when resolved to ≤ Grade 1 [see Dosage and Administration (2.3) ].
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 TRODELVY (e.g., abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., atropine) for subsequent treatments.
5.3Hypersensitivity and Infusion-Related Reactions
TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions [see Contraindications (4) ] . Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients treated with TRODELVY. Grade 3–4 hypersensitivity occurred in 2% of patients treated with TRODELVY.
The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Premedication for infusion reactions in patients receiving TRODELVY is recommended . Have medications and emergency equipment to treat infusion-related reactions, including anaphylaxis, available for immediate use when administering TRODELVY [see Dosage and Administration (2.2) ].
Closely monitor patients for hypersensitivity and infusion-related reactions during each TRODELVY infusion and for at least 30 minutes after completion of each infusion [see Dosage and Administration (2.3) ] . Permanently discontinue TRODELVY for Grade 4 infusion-related reactions [see Dosage and Administration (2.3) ] .
5.4Nausea and Vomiting
TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY. Grade 3–4 nausea occurred in 3% of patients. Vomiting occurred in 35% of all patients treated with TRODELVY. 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 NK 1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV) [ see Dosage and Administration (2.2) ].
Withhold TRODELVY 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 [see Dosage and Administration (2.3) ]. 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.
5.5Increased 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 when treated with TRODELVY. The incidence of neutropenia and anemia was analyzed in 948 patients who received TRODELVY and had UGT1A1 genotype results. In patients homozygous for the UGT1A1 *28 allele (n=112), the incidence of Grade 3–4 neutropenia was 58%.
In patients heterozygous for the UGT1A1*28 allele (n=420), the incidence of Grade 3–4 neutropenia was 49%. In patients homozygous for the wild-type allele (n=416), the incidence of Grade 3–4 neutropenia was 43% [see Clinical Pharmacology (12.5) ] . In patients homozygous for the UGT1A1 *28 allele, the incidence of Grade 3–4 anemia was 21%. In patients heterozygous for the UGT1A1*28 allele, the incidence of Grade 3–4 anemia was 10%.
In patients homozygous for the wild-type allele, the incidence of Grade 3–4 anemia was 9%. The median time to first neutropenia including febrile neutropenia was 9 days in patients homozygous for the UGT1A1*28 allele, 15 days in patients heterozygous for the UGT1A1*28 allele, and 20 days in patients homozygous for the wild-type allele. The median time to first anemia was 21 days in patients homozygous for the UGT1A1*28 allele, 25 days in patients heterozygous for the UGT1A1*28 allele, and 28 days 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 enzyme activity [see Dosage and Administration (2.3) ].
5.6Embryo-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 [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ]. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to us
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Interactions
UGT1A1 inhibitors or inducers: Avoid concomitant use. ( 7 )
7.1Effect of Other Drugs on
TRODELVY 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 [see Warning and Precaution (5.5) and Clinical Pharmacology (12.3 , 12.5) ] . Avoid administering UGT1A1 inhibitors with TRODELVY. UGT1A1 Inducers Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers [see Warning and Precaution (5.5) and Clinical Pharmacology (12.3 , 12.5) ] .
Avoid administering UGT1A1 inducers with TRODELVY.
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary Based
on its mechanism of action, TRODELVY 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. TRODELVY contains a genotoxic component, SN-38, and is toxic to rapidly dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ] . 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. Data Animal data There were no reproductive and developmental toxicology studies conducted with sacituzumab govitecan-hziy.
Adverse reactions
The following adverse reactions are discussed in greater detail in other sections of the label: Neutropenia [see Warnings and Precautions (5.1) ] Diarrhea [see Warnings and Precautions (5.2) ] Hypersensitivity and Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Nausea and Vomiting [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence ≥25%) are (including laboratory abnormalities) were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, diarrhea, nausea, decreased lymphocyte count, fatigue, alopecia, constipation, increased glucose, decreased albumin, vomiting, decreased appetite, decreased creatinine clearance, increased alkaline phosphatase, decreased magnesium, decreased potassium, and decreased sodium.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-888-983-4668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The pooled safety population described in the Warnings and Precautions section reflect exposure to TRODELVY in 1063 patients, which included 366 patients with mTNBC and 322 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer from IMMU-132-01, ASCENT, and TROPiCS-02; and 375 patients with other tumor types.
TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. Among the 1063 patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 63 months). In this 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%).
Locally Advanced or Metastatic Triple-Negative Breast Cancer ASCENT Study The safety of TRODELVY was evaluated in a randomized, active-controlled, open-label study (ASCENT) in patients with mTNBC who had previously received a taxane and at least two prior chemotherapies. Patients were randomized (1:1) to receive either TRODELVY (n=258) or single agent chemotherapy (n=224) and were treated until disease progression or unacceptable toxicity [see Clinical Studies (14.1) ] .
For patients treated with TRODELVY, the median duration of treatment was 4.4 months (range: 0 to 23 months). Serious adverse reactions occurred in 27% of patients receiving TRODELVY. Serious adverse reactions in > 1% of patients receiving TRODELVY included neutropenia (7%), diarrhea (4%), and pneumonia (3%). Fatal adverse reactions occurred in 1.2% of patients who received TRODELVY, including respiratory failure (0.8%) and pneumonia (0.4%).
TRODELVY was permanently discontinued for adverse reactions in 5% of patients. Adverse reactions leading to permanent discontinuation in ≥ 1 % of patients who received TRODELVY were pneumonia (1%) and fatigue (1%). Adverse reactions leading to a treatment interruption of TRODELVY occurred in 63% of patients. The most frequent (≥5%) adverse reactions leading to a treatment interruption were neutropenia (47%), diarrhea (5%), respiratory infection (5%), and leukopenia (5%).
Adverse reactions leading to a dose reduction of TRODELVY occurred in 22% of patients. The most frequent (>4%) adverse reactions leading to a dose reduction were neutropenia (11%) and diarrhea (5%). Granulocyte-colony stimulating factor (G-CSF) was used in 44% of patients who received TRODELVY. Tables 3 and 4 summarize adverse reactions and laboratory abnormalities, respectively, in the ASCENT study. Table 3: Adverse Reactions in ≥ 10% of Patients with mTNBC in ASCENT TRODELVY (n=258) Single Agent Chemotherapy (n=224) Adverse Reaction All Grades % Grade 3 – 4 % All Grades % Grade 3 – 4 % *Single agent chemotherapy included one of the following single-agents: eribulin (n=139), capecitabine (n=33), gemcitabine (n=38), or vinorelbine (except if patient had ≥ Grade 2 neuropathy, n=52).
0.5 Increased lactate dehydrogenase 18 0 22 0 Decreased glucose 10 0 3.2 0 Study IMMU-132-01 The safety of TRODELVY was evaluated in a single-arm, open-label study (IMMU-132-01) in patients with mTNBC and other malignancies, which included 108 patients with mTNBC who had received at least two prior anticancer therapies for metastatic disease [see Clinical Studies (14.1) ] . TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses up to 10 mg/kg until disease progression or unacceptable toxicity.
The median treatment duration in these 108 patients was 5.1 months (range: 0 to 51 months). Serious adverse reactions occurred in 31% of the patients. Serious adverse reactions in > 1% of patients receiving TRODELVY included febrile neutropenia (6%) vomiting (5%), nausea (3%), dyspnea (3%), diarrhea (4%), anemia (2%), pleural effusion, neutropenia, pneumonia, dehydration (each 2%). TRODELVY was permanently discontinued for adverse reactions in 2% of patients.
Adverse reactions leading to permanent discontinuation were anaphylaxis, anorexia/fatigue, headache (each 0.9%). Forty- five percent (45%) of patients experienced an adverse reaction leading to treatment interruption. The most common adverse reaction leading to treatment interruption was neutropenia (33%). Adverse reactions leading to dose reduction occurred in 33% of patients treated with TRODELVY, with 24% having one dose reduction, and 9% with two dose reductions.
The most common adverse reaction leading to dose reductions was neutropenia/febrile neutropenia. Tables 5 and 6 summ
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
SACITUZUMAB GOVITECAN-HZIY 180MG
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application BLA761115.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
