Established safety profile of TRODELVY
Adverse reactions reported in ≥15% (Grade 1-4) or ≥5% (Grade ≥3) of patients treated with TRODELVY (n=113)1
| Adverse reaction | Grade 1-4 (%) | Grade 3-4 (%) |
|---|---|---|
| Any adverse reaction | 94 | 80 |
| Adverse reaction | Grade 1-4 (%) | Grade 3-4 (%) |
|---|---|---|
| Any adverse reaction | 94 | 80 |
| Diarrhea | 72 | 12 |
| Nausea | 66 | 4 |
| Constipation | 34 | 1 |
| Vomiting | 34 | 1 |
| Abdominal paini | 31 | 2 |
| Fatigueii | 68 | 5 |
| Pyrexia | 19 | 0 |
| Edemaiii | 17 | 2 |
| Alopecia | 49 | 0 |
| Rashiv | 32 | 2 |
| Decreased appetite | 41 | 3 |
| Weight lossv | 17 | 2 |
| Acute kidney injuryvi | 24 | 7 |
| Hematuria | 16 | 1 |
| Any infectionvii | 50 | 25 |
| Urinary tract infection | 19 | 12 |
| Coughviii | 17 | 0 |
| Dyspnea | 16 | 0 |
| Back Pain | 16 | 0 |
| Venous thromboembolismix | 9 | 6 |
Graded per NCI CTCAE v5.0.
i Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain.
ii Includes fatigue and asthenia.
iii Includes edema genital, edema peripheral, peripheral swelling.
iv Includes dermatitis acneiform, dermatitis bullous, erythema, lichen planus, photosensitivity reaction, pruritus, pruritus generalised, rash, rash macular, rash maculo-papular, rash pruritic, skin papilloma, skin toxicity.
v Includes failure to thrive and weight decreased.
vi Includes acute kidney injury, blood creatinine increased, nephropathy toxic, renal failure, renal impairment.
vii Includes bacteremia, body tinea, bronchitis, candida infection, cellulitis, clostridium difficile infection, coronavirus infection, device related infection, diverticulitis, escherichia bacteremia, escherichia pyelonephritis, folliculitis, gastroenteritis, gastroenteritis escherichia coli, herpes zoster, kidney infection, klebsiella sepsis, lung infection, nasopharyngitis, oral candidiasis, oral herpes, pneumonia, pyelonephritis, pyelonephritis acute, respiratory tract infection, rhinitis, sepsis, sinusitis, skin infection, tooth abscess, upper respiratory tract infection, urinary tract infection, urosepsis, vascular device infection, viral infection, viral pharyngitis, vulvovaginal mycotic infection.
viii Includes cough, productive cough, upper-airway cough syndrome.
ix Includes deep vein thrombosis, embolism, and pulmonary embolism.
Additional safety information
- Serious adverse reactions occurred in 44% of patients receiving TRODELVY
- Serious adverse reactions in >1% of patients receiving TRODELVY included infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), sepsis or bacteremia (5%), diarrhea (4%), anemia, venous thromboembolism, and small intestinal obstruction (3% each), pneumonia, abdominal pain, pyrexia, and thrombocytopenia (2% each)
- Fatal adverse reactions occurred in 3.6% of patients, including sepsis, respiratory failure, epistaxis, and completed suicide
- Adverse reactions leading to permanent discontinuation of TRODELVY occurred in 10% of patients
- The most frequent adverse reaction leading to permanent discontinuation of study drug was neutropenia (4%, including febrile neutropenia in 2%)
- Adverse reactions leading to dose interruption of TRODELVY occurred in 52% of patients
- The most common adverse reactions leading to dose interruption were neutropenia (27%, including febrile neutropenia in 2%), infection (12%), and acute kidney injury (8%)
- Adverse reactions leading to a dose reduction of TRODELVY occurred in 42% of patients. The most common (>4%) adverse reactions leading to a dose reduction were neutropenia (13%, including febrile neutropenia in 3%), diarrhea (11%), fatigue (8%), and infection (4%)
- Granulocyte colony-stimulating factor (G-CSF) was used in 47% of patients who received TRODELVY
- The most common (≥25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (78%), diarrhea (72%), decreased hemoglobin (71%), decreased lymphocyte count (71%), fatigue (68%), decreased neutrophil count (67%), nausea (66%), increased glucose (59%), decreased albumin (51%), any infection (50%), alopecia (49%), decreased calcium (46%), decreased sodium (43%), decreased appetite (41%), decreased phosphate (41%), increased alkaline phosphatase (36%), constipation (34%), vomiting (34%), increased activated partial thromboplastin time (33%), increased creatinine (32%), rash (32%), decreased magnesium (31%), abdominal pain (31%), increased alanine aminotransferase (28%), increased lactate dehydrogenase (28%), decreased potassium (27%), increased aspartate aminotransferase (26%), and decreased platelet count (25%)
- Other clinically significant adverse reactions (≤15%) include peripheral neuropathy (12%), sepsis or bacteremia (9%), and pneumonia (4%)
- Cases of Grade 3-4 neuropathy were not reported in Cohort 1 of TROPHY
Selected laboratory abnormalities reported in ≥20% (any grade) or ≥5% (Grade 3–4) of patients treated with TRODELVY (n=113)1
| Adverse reaction | Any gradex (%) |
Grade 3-4x (%) |
|---|
| Adverse reaction | Any gradex (%) |
Grade 3-4x (%) |
|---|---|---|
| Decreased leukocyte count | 78 | 38 |
| Decreased lymphocyte count | 71 | 35 |
| Decreased hemoglobin | 71 | 18 |
| Decreased neutrophil count | 67 | 43 |
| Decreased platelet count | 25 | 2 |
| Increased glucose | 59 | 8 |
| Decreased albumin | 51 | 4 |
| Decreased calcium | 46 | 9 |
| Decreased sodium | 43 | 1 |
| Decreased phosphate | 41 | 15 |
| Increased alkaline phosphatase | 36 | 0 |
| Increased creatinine | 32 | 5 |
| Decreased magnesium | 31 | 2 |
| Increased alanine aminotransferase | 28 | 2 |
| Increased lactate dehydrogenase | 28 | 0 |
| Decreased potassium | 27 | 0 |
| Increased aspartate aminotransferase | 26 | 2 |
| Increased alkaline phosphatase | 36 | 0 |
| Increased creatinine | 32 | 5 |
| Decreased magnesium | 31 | 2 |
| Increased alanine aminotransferase | 28 | 2 |
| Increased lactate dehydrogenase | 28 | 0 |
| Decreased potassium | 27 | 0 |
| Increased aspartate aminotransferase | 26 | 2 |
| Increased activated partial thromboplastin time | 33 | 6 |
xDenominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available (range: 66–111 patients).
Explore safety data from the TROPHY study with investigator Petros Grivas, MD, PhD
References: 1. TRODELVY [package insert]. Foster City, CA: Gilead Sciences, Inc.; February 2023. 2. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021;39(22):2474-2485.
TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
- 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 TROPHY study, the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY 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.