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
The ASCENT study demonstrated a well-characterized safety profile for TRODELVY
Adverse reactions in ≥10% of patients with mTNBC in the ASCENT study1
|
TRODELVY (n=258) |
Single-agent chemotherapya (n=224) |
|||
|---|---|---|---|---|
| Adverse reaction |
All grades (%) |
Grades 3-4 (%) |
All grades (%) |
Grades 3-4 (%) |
| Diarrhea | 59 | 11 | 17 | 1 |
| Nausea | 57 | 3 | 26 | 0.4 |
| Vomiting | 33 | 2 | 16 | 1 |
| Constipation | 37 | 0.4 | 23 | 0 |
| Abdominal pain | 30 | 3 | 12 | 1 |
| Stomatitisb | 17 | 2 | 13 | 1 |
| Fatiguec | 65 | 6 | 50 | 9 |
| Pyrexia | 15 | 0.4 | 14 | 2 |
| Urinary tract infection | 13 | 0.4 | 8 | 0.4 |
| Upper respiratory tract infection | 12 | 0 | 3 | 0 |
| Decreased appetite | 28 | 2 | 21 | 1 |
| Back pain | 16 | 1 | 14 | 2 |
| Arthralgia | 12 | 0.4 | 7 | 0 |
| Headache | 18 | 0.8 | 13 | 0.4 |
| Dizziness | 10 | 0 | 7 | 0 |
| Insomnia | 11 | 0 | 5 | 0 |
| Cough | 24 | 0 | 18 | 0.4 |
| Alopecia | 47 | 0 | 16 | 0 |
| Rash | 12 | 0.4 | 5 | 0.4 |
| Pruritus | 10 | 0 | 3 | 0 |
Graded per NCI CTCAE v.5.0.1
aSingle-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).1
bIncluding stomatitis, glossitis, mouth ulceration, and mucosal inflammation.1
cIncluding fatigue and asthenia.1
NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.
Additional safety information
- 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%)
- The most common (≥25%) adverse reactions in ASCENT, including lab abnormalities, were decreased hemoglobin (94%), decreased lymphocyte count (88%), decreased leukocyte count (86%), decreased neutrophil count (78%), fatigue (65%), diarrhea (59%), nausea (57%), increased glucose (49%), alopecia (47%), constipation (37%), decreased calcium (36%), vomiting (33%), decreased magnesium (33%), decreased potassium (33%), increased albumin (32%), abdominal pain (30%), decreased appetite (28%), increased aspartate aminotransferase (27%), increased alanine aminotransferase (26%), increased alkaline phosphatase (26%), and decreased phosphate (26%)
- In the pooled safety population (N=1063), 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%)
- Adverse reactions leading to permanent discontinuation of TRODELVY occurred 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 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 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
Laboratory abnormalities in >10% of patients with mTNBC in ASCENT1
|
TRODELVY (n=258) |
Single-agent chemotherapya (n=224) |
|||
|---|---|---|---|---|
| Laboratory abnormality |
All grades (%) |
Grade 3-4 (%) |
All grades (%) |
Grade 3-4 (%) |
| Hematology | ||||
| Decreased hemoglobin | 94 | 9 | 57 | 6 |
| Decreased lymphocyte count | 88 | 31 | 40 | 24 |
| Decreased leukocyte count | 86 | 41 | 53 | 25 |
| Decreased neutrophil count | 78 | 49 | 48 | 36 |
| Decreased platelet count | 23 | 1.2 | 25 | 2.7 |
| Chemistry | ||||
| Increased glucose | 49 | 2.3 | 43 | 2.8 |
| Decreased calcium | 36 | 1.6 | 21 | 1.4 |
| Decreased magnesium | 33 | 0.4 | 20 | 0 |
| Decreased potassium | 33 | 4.3 | 28 | 0.9 |
| Increased albumin | 32 | 0.8 | 25 | 1.4 |
| Increased aspartate aminotransferase | 27 | 1.2 | 32 | 1.4 |
| Increased alanine aminotransferase | 26 | 1.2 | 26 | 1.8 |
| Increased alkaline phosphatase | 26 | 0 | 17 | 0.5 |
| Decreased phosphate | 26 | 7.8 | 20 | 3.3 |
| Decreased sodium | 22 | 0.4 | 17 | 0.5 |
| Increased lactate dehydrogenase | 18 | 0 | 22 | 0 |
| Decreased glucose | 10 | 0 | 3.2 | 0 |
aSingle-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). Graded per NCI CTCAE v.5.0.
Explore dosing and safety with Sara Tolaney, MD, MPH, in the video below
Reference: 1. TRODELVY [package insert]. Foster City, CA: Gilead Sciences, Inc.; February 2023.
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.
- 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, 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.
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.