Nearly 30% of patients responded to treatment with TRODELVY1
ORR by IRA based on RECIST 1.1†
In the TROPHY study, TRODELVY demonstrated a median DOR of more than 7 months1
Median DOR by IRA based on RECIST 1.1
0.0
months
(range 1.4+, 13.7)
(95% CI: 4.7-8.6)
# of responders: 31
+: denotes ongoing
ORR with TRODELVY was in select subgroups†‡
In Cohort 1 of the TROPHY study
Number of prior therapies for metastatic disease2
≤2
0.0 %
(n/N=10/36;
95% CI: 14.2-45.2)
>2
0.0 %
(n/N=21/77;
95% CI: 17.7-38.6)
Presence of visceral metastases2
With
0 . 9 %
(n/N=21/75;
95% CI: 18.2-39.6)
Without
0.0 %
(n/N=10/38;
95% CI: 13.4-43.1)
Presence of visceral liver metastases2
With
0.0 %
(n/N=12/38;
95% CI: 17.5-48.6)
Without
0.0 %
(n/N=19/75;
95% CI: 16.0-36.7)
Important limitations:
- The results of this exploratory subgroup analysis should be interpreted with caution due to the lack of formal statistical testing and modest patient numbers in each subgroup. These data are descriptive and should not be used to draw conclusions
- Subgroup analyses include all treated patients, defined as all enrolled patients who had received at least 1 dose of TRODELVY
- Subgroup data are not included in the Prescribing Information for TRODELVY
†ORR consisted of confirmed CR and PR per RECIST 1.1 as evaluated by independent review assessment. CR was defined as the disappearance of all target and nontarget lesions. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.3
‡Median follow up was 9.1 months (range 0-19.9).
Change in individual patient target lesion measurement per BICR in Cohort 1 of the TROPHY study2
In Cohort 1 of the TROPHY study, the major efficacy outcome measures were ORR (consisting of confirmed CR and PR) and DOR evaluated by IRA based on RECIST 1.1 criteria.2,3§
Important limitations:
- Bars represent best percent change from baseline in the sum of the diameters of the target lesions and may not correspond with the Best Overall Response (BOR), which is based on target and non-target lesions’ response to treatment. Bars that fall below the x-axis represent target lesions with a response of CR, PR, or stable disease (SD) in which target lesions decreased in size more than 0% but less than 30%. Based on RECIST v1.1, SD was defined as neither sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as ≥20% increase in the sum of the diameters of the target lesions, taking as reference the smallest sum
- Not every bar that falls below the x-axis represents a CR or PR (ie, confirmed objective response), and these results should be interpreted with caution as they may reflect the natural history of the disease rather than any treatment effect
- Changes in individual patients’ target lesions data are not included in the Prescribing Information for TRODELVY
Best percent change from baseline in patient target lesion diametersa-c
aBars represent best percent change from baseline in the sum of the diameters of the target lesions (longest for non-nodal and short axis for nodal lesions) in 94 patients with at least 1 postbaseline target lesion measurement. These data include all treated patients, defined as all enrolled patients who had received at least 1 dose of study drug. Data exclude 19 patients due to no postbaseline radiologic assessments (n=15), or incomplete assessment of target lesions at baseline or postbaseline (n=4).
bThe dashed lines at +20% and −30% indicate thresholds of progressive disease and PR, respectively, according to RECIST 1.1 criteria.
cThe change in target lesion size may not account for new lesions.
§CR was defined as the disappearance of all target and non-target lesions. PR was defined as ≥30% decrease in the sum of the diameters of the target lesions, taking as reference the baseline sum of diameters.
Noncomparative analysis of median PFS and OS in TROPHY (Cohort 1)2||
Important limitations:
- The accelerated approval of TRODELVY for this indication was based on ORR and DOR. PFS and OS were secondary endpoints in Cohort 1 of the TROPHY study and this data has not been reviewed by the FDA. Single-arm studies cannot adequately characterize time-to-event endpoints such as PFS and OS. As such, the clinical significance of these data are not known and these analyses should be interpreted with caution
- These data include all treated patients, defined as all enrolled patients who had received at least 1 dose of TRODELVY
- OS and PFS data are not included in the Prescribing Information for TRODELVY
Median PFS
0.0
months
(95% CI: 3.5-7.2)
Median OS
0.0
months
(95% CI: 9.0-13.8)
TRODELVY 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 a confirmatory trial.
||Based on Kaplan-Meier estimate of data with a median duration of follow-up of 9.1 months with a data cutoff date of September 18, 2020.
Delve more deeply into the results of the TROPHY study with investigator Scott T. Tagawa, MD, PhD
BICR=blinded, independent, central review; CI=confidence interval; CR=complete response; DOR=duration of response; IRA=independent review assessment; mUC=metastatic urothelial cancer; ORR=objective response rate; OS=overall survival; PD-1=programmed death receptor-1; PD-L1=programmed death-ligand 1; PFS=progression-free survival; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors.
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. 3. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
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.