Trodelvy® (sacituzumab govitecan-hziy)
ASCENT Study in Metastatic Triple-Negative Breast Cancer
Gilead Sciences, Inc. is providing this document to you, a US Healthcare Professional, in response to your unsolicited request for medical information.
Gilead Sciences, Inc. is providing this document to you, a US Healthcare Professional, in response to your unsolicited request for medical information.
Trodelvy® (sacituzumab govitecan-hziy)
ASCENT Study in mTNBC
This document is in response to your request for information regarding Trodelvy® (sacituzumab govitecan-hziy [SG]) and the phase 3 ASCENT trial in patients with metastatic triple-negative breast cancer (mTNBC).
Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.
The full indication, important safety information, and boxed warnings for neutropenia and diarrhea are available at:
www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.
Summary
Relevant Product Labeling1
SG is indicated for the treatment of adult patients with unresectable locally advanced or mTNBC who have received ≥2 prior systemic therapies, ≥1 of them for metastatic disease.
The phase 3 ASCENT study evaluated the efficacy and safety of SG or single-agent chemotherapy in BMNeg and BMPos patients positive for brain metastasis (stable, previously treated) with locally advanced or mTNBC who relapsed after ≥2 prior chemotherapies.2
- SG prolonged the median PFS (primary endpoint; BMNeg population) in comparison with chemotherapy (5.6 vs 1.7 months; P<0.001).2
- The rates of OS were greater in the SG group than in the chemotherapy group (BMNeg population median OS: 12.1 vs 6.7 months; P<0.001).2
- The ORR (35% vs 5%) and the CR (4% vs 1%) and PR (31% vs 4%) rates were greater in the SG group than in the chemotherapy group in the BMNeg population.2
- A similar clinical benefit in PFS and OS was observed in the full study population of BMPos and BMNeg patients.2
- Updated results from the final database lock (February 25, 2021) demonstrated efficacy and safety results consistent with the previous analysis from the March 2020 data cut for the BMNeg population.3
- In an ad hoc subgroup analysis of the impact of BMI on the safety and efficacy of SG, SG was associated with a longer PFS and OS and a higher ORR and CBR than TPC across all evaluated BMI subgroups (<25 kg/m2, 25 to <30 kg/m2, and ≥30 kg/m2).4
ASCENT Study on SG in mTNBC
Study Design and Demographics2
ASCENT, a global, open‑label, randomized, confirmatory, phase 3 study, was conducted to investigate the efficacy and safety of SG vs TPC in patients with refractory or relapsed mTNBC who had received ≥2 prior chemotherapies for unresectable, locally advanced, or metastatic disease.
A total of 529 patients with mTNBC were enrolled and randomly assigned (1:1) to receive SG (n=267) or single-agent chemotherapy (n=262; eribulin, vinorelbine, capecitabine, or gemcitabine; Figure 1). The primary endpoint was PFS in BMNeg patients at baseline, as measured by a BICR. See Figure 1 for key secondary endpoints.
Figure 1. ASCENT Study Design2
Abbreviations: ASCO=American Society of Clinical Oncology; CAP=College of American Pathologists; ECOG PS=Eastern Cooperative Oncology Group Performance Status; R=randomized; TNBC=triple-negative breast cancer.
aTNBC diagnosis determined per ASCO/CAP guidelines. mTNBC was histologically or cytologically confirmed.
bHad stable central nervous system disease for ≥4 weeks and could use stable, low-dose corticosteroids (≤20 mg of prednisone/prednisolone or equivalent). Their data were not included in the primary endpoint analysis.
cMRIs to determine baseline brain metastases were required only for patients with known brain metastases, and imaging (MRI or CT scans) was conducted every 6 weeks for 36 weeks and every 9 weeks thereafter (until disease progression led to study treatment discontinuation); confirmatory imaging was performed 4 to 6 weeks later.
Due to compelling evidence of efficacy with SG treatment, the ASCENT study was halted early in March 2020. The primary analysis population included 235 BMNeg patients in the SG group and 233 BMNeg patients in the TPC group (54% received eribulin, 20% received vinorelbine, 13% received capecitabine, and 12% received gemcitabine); 61 patients had stable, pretreated brain metastases at baseline and were not included in the primary analysis population. Seven patients in the SG group and 32 patients in the TPC group did not receive their assigned treatment or withdrew before treatment consent; their data were included in the efficacy analysis but not in the safety analysis.
At the final data cut (March 11, 2020), the median (range) duration of follow-up was 17.7 (5.8–28.1) months, and patients had received a median of 7 treatment cycles of SG, with a median treatment duration (range) of 4.4 (0.03–22.9) months; patients in the TPC group had a median of 3, 2, 2, and 2 cycles of eribulin, vinorelbine, gemcitabine, and capecitabine, respectively, for median treatment durations of 1.6, 1, 1.4, and 1.2 months (data from 6 patients who received capecitabine were unavailable).
Efficacy Results2
PFS
The BICR analysis demonstrated that treatment with SG, in comparison with TPC, significantly prolonged the median PFS (HR: 0.41; 95% CI: 0.32–0.52; P<0.001). The median PFS for BMNeg patients (primary endpoint) treated with SG was 5.6 months (95% CI: 4.3–6.3; 166 events), compared with 1.7 months (95% CI: 1.5–2.6; 150 events) for those treated with chemotherapy. The median PFS rates determined through central review were similar to those determined by investigator assessments: 5.5 months in the SG group and 1.7 months in the TPC group (HR: 0.35; 95% CI: 0.28–0.44). Within the BMNeg cohort, subgroup analyses of PFS were also evaluated.
Secondary endpoints
Table 1. ASCENT Study: Summary of Treatment Efficacy (per BICR)2
Variable | BMNeg | Full Population | ||
SG (n=235) | TPC (n=233) | SG (n=267) | TPC (n=262) | |
PFS, median (95% CI), mo | 5.6 (4.3–6.3) | 1.7 (1.5–2.6) | 4.8 (4.1–5.8) | 1.7 (1.5–2.5) |
HR for disease progression or death (95% CI) | 0.41 (0.32–0.52); P<0.001 | 0.43 (0.35−0.54) | ||
OS, median (95% CI), mo | 12.1 (10.7–14) | 6.7 (5.8–7.7) | 11.8 (10.5–13.8) | 6.9 (5.9–7.7) |
HR for death (95% CI) | 0.48 (0.38–0.59); P<0.001 | 0.51 (0.41–0.62) | ||
ORR,a n (%) | 82 (35) | 11 (5) | 83 (31) | 11 (4) |
CR, n (%) | 10 (4) | 2 (1) | 10 (4) | 2 (1) |
PR, n (%) | 72 (31) | 9 (4) | 73 (27) | 9 (3) |
CBR,b n (%) | 105 (45) | 20 (9) | 108 (40) | 21 (8) |
SD, n (%) | 81 (34) | 62 (27) | 96 (36) | 71 (27) |
SD for ≥6 mo, n (%) | 23 (10) | 9 (4) | 25 (9) | 10 (4) |
Progressive disease, n (%) | 54 (23) | 89 (38) | 65 (24) | 100 (38) |
Response could not be evaluated,c n (%) | 18 (8) | 71 (30) | 23 (9) | 80 (31) |
Time-to-response, median (95% CI), mo | 1.5 (0.7–10.6) | 1.5 (1.3–4.2) | 1.5 (0.7–10.6) | 1.5 (1.3–4.2) |
DOR, median (95% CI), mo | 6.3 (5.5–9) | 3.6 (2.8–NE) | 6.3 (5.5–9) | 3.6 (2.8–NE) |
HR (95% CI) | 0.39 (0.14–1.07) | – | ||
Abbreviation: NE=not evaluable.
aThe ORR was defined as a CR or PR.
bThe CBR was defined as CR, PR, or SD with a duration of ≥6 months.
cReasons include missing post-baseline images or having unreadable images.
Safety2
The most common Grade ≥3 TRAEs in the SG group and the TPC group included neutropenia (51% and 33%, respectively), diarrhea (10% and <1%), leukopenia (10% and 5%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). Dose reductions occurred in 22% of patients in the SG group and in 26% of patients in the TPC group. AEs that led to treatment discontinuation occurred in 5% of patients in each group. Serious TRAEs occurred in 39 patients (15%) in the SG group and in 19 patients (8%) in the TPC group.
Among those who received SG, ocular toxicity occurred in 5% of patients (none of the events were Grade >1), and no Grade >2 neuropathy was observed. One patient in the SG group developed Grade 3 pneumonitis, and no Grade 1 or 2 events of interstitial lung disease were observed. Three non–treatment-related deaths occurred in the SG group (respiratory failure, n=2; post-obstructive pneumonia, n=1). Three deaths also occurred in the TPC group; of these, 1 treatment-related death due to neutropenic sepsis was reported.
Table 2. ASCENT Study: TRAEs (Any-Grade AE in ≥10% of Patients ; Grade 3/4 AEs in ≥5% of Patients ) in the Safety Population2
AEs, n (%) | SG (n=258) | TPC (n=224) | |||||
Any | Grade 3 | Grade 4 | Any | Grade 3 | Grade 4 | ||
Any AE | 252 (98) | 117 (45) | 48 (19) | 192 (86) | 71 (32) | 33 (15) | |
Hematologic | Neutropeniaa | 163 (63) | 88 (34) | 44 (17) | 96 (43) | 45 (20) | 29 (13) |
Anemiab | 89 (34) | 20 (8) | 0 | 54 (24) | 11 (5) | 0 | |
Leukopeniac | 41 (16) | 23 (9) | 3 (1) | 25 (11) | 10 (4) | 2 (1) | |
Thrombocytopeniad | 14 (5) | 2 (1) | 2 (1) | 25 (11) | 3 (1) | 0 | |
Febrile neutropenia | 15 (6) | 12 (5) | 3 (1) | 5 (2) | 4 (2) | 1 (<1) | |
Gastrointestinal | Diarrhea | 153 (59) | 27 (10) | 0 | 27 (12) | 1 (<1) | 0 |
Nausea | 147 (57) | 6 (2) | 1 (<1) | 59 (26) | 1 (<1) | 0 | |
Vomiting | 75 (29) | 2 (1) | 1 (<1) | 23 (10) | 1 (<1) | 0 | |
Constipation | 44 (17) | 0 | 0 | 32 (14) | 0 | 0 | |
Abdominal pain | 29 (11) | 3 (1) | 0 | 9 (4) | 1 (<1) | 0 | |
General disorders and administration site conditions | Fatigue | 115 (45) | 8 (3) | 0 | 68 (30) | 12 (5) | 0 |
Asthenia | 31 (12) | 2 (1) | 0 | 23 (10) | 3 (1) | 0 | |
Skin and subcutaneous disorderse | Alopecia | 119 (46) | 0 | 0 | 35 (16) | 0 | 0 |
Metabolism and | Decreased appetite | 51 (20) | 4 (2) | 0 | 32 (14) | 1 (<1) | 0 |
Nervous system disordersf,g | 64 (25) | 1 (<1) | 0 | 53 (24) | 5 (2) | 0 | |
Respiratory, thoracic, and mediastinal disordersg | 41 (16) | 5 (2) | 0 | 17 (8) | 1 (<1) | 0 | |
Musculoskeletal and connective disordersg | 32 (12) | 0 | 0 | 28 (12) | 3 (1) | 0 | |
Infections and infestationsg,h | 30 (12) | 6 (2) | 1 (<1) | 22 (10) | 4 (2) | 3 (1) | |
aIncluded neutropenia and decreased neutrophil count.
bIncluded anemia, Hgb decreased, and decreased RBC count.
cIncluded leukopenia and decreased WBC count.
dIncluded thrombocytopenia and decreased platelet count.
eThere was one Grade 3 rash in each of the SG and TPC groups.
fThere were no Grade 3/4 neuropathy events with SG. In the TPC group, there were Grade 3 AEs of peripheral neuropathy (n=2) and peripheral sensory neuropathy (n=2).
gFor this category, the overall any-grade AE rate was ≥10%, but the rate of all individual any-grade AEs was ≤5%.
hThere was 1 case of Grade 3 pneumonitis in the SG group and none in the TPC group.
Updated Results From the Final Database Lock3
The final database lock date (February 25, 2021) included efficacy and safety data from an additional 17 patients after the final data cut.
Results of the follow-up analysis were consistent with those from the previous analysis from the March 2020 final data cut. In the BMNeg population, the median PFS was 5.6 months (95% CI: 4.3–6.3) in the SG group and 1.7 months (95% CI: 1.5–2.6) in the TPC group (HR: 0.39; P<0.0001). Since the previous analysis in the BMNeg population, 1 additional PFS event occurred in the SG group (number of events: SG group, n=167; TPC group, n=150). Results for OS, ORR, CBR, DOR, and time-to-response were similar to or unchanged from those in the previous analysis. The 24-month OS rates in the BMNeg population were 22.4% (95% CI: 16.8–28.5) in the SG group and 5.2% (95% CI: 2.5–9.4) in the TPC group. The 24‑month OS rates were similar in the overall ITT population: 20.5% (95% CI: 15.4–26.1) in the SG group and 5.5% (95% CI: 2.8–9.4) in the TPC group.
AEs led to treatment discontinuation in 6 patients (3%) in the SG group and 7 patients (3%) in the TPC group. No additional treatment‑related deaths occurred, and the incidence of TRAEs was consistent with that in the previous analysis.
Ad Hoc Subgroup Analysis: Impact of BMI on the Safety and Efficacy of SG4
An ad hoc subgroup analysis was conducted among patients from the ITT population (N=528) who received either SG or TPC to assess the impact of BMI on the safety and efficacy of SG; dosage was not capped for high BMI. Overall, 241/528 patients (46%) were underweight/normal, 155/528 patients (29%) were overweight (BMI 25 to <30 kg/m2), and 132/528 (25%) were obese (BMI ≥30 kg/m2).
At the data cutoff of February 25, 2021, SG was associated with a longer PFS and OS and a higher ORR and CBR than TPC across all BMI subgroups (Table 3 and Table 4).
Table 3. ASCENT Subgroup Analysis: PFS by Independent Review and OS Results by BMI Subgroup4
BMI Subgroup | SG | TPC | HR (95% CI) | P-Value | |
PFS, median (95% CI), months | Underweight/normal (n=241) | 4.2 (2.9–5.6) | 1.9 (1.5–2.8) | 0.503 (0.366–0.692) | <0.0001 |
Overweight (n=155) | 4.6 (3.3–6.3) | 1.5 (1.4–1.6) | 0.310 (0.203–0.473) | <0.0001 | |
Obese (n=132) | 5.9 (4.1–8.3) | 2.6 (1.6–3) | 0.337 (0.212–0.534) | <0.0001 | |
OS, median (95% CI), months | Underweight/normal (n=241) | 10.9 (9.4–13) | 6.2 (4.8–7.1) | 0.554 (0.418–0.735) | <0.0001 |
Overweight (n=155) | 10.8 (9–14.2) | 6.7 (5.2–8.9) | 0.511 (0.354–0.735) | 0.0003 | |
Obese (n=132) | 14.9 (11.2–16.8) | 8.7 (6.7–9.8) | 0.451 (0.304–0.67) | <0.0001 | |
Table 4. ASCENT Subgroup Analysis: ORR and CBR by Independent Review4
Underweight/Normal | Overweight | Obese | ||||
SG | TPC | SG | TPC | SG | TPC | |
ORR,a % (95% CI) | 25 (18–34) | 8 (4–15) | 34 (23–46) | 1 (0–7) | 40 (28–52) | 2 (0–8) |
OR (95% CI) | 3.9 (1.8–8.7) | 42.4 (5.6–323.4) | 41.5 (5.4–317.3) | |||
CBR,b % (95% CI) | 35 (27–44) | 11 (6–19) | 41 (29–53) | 5 (1–12) | 50 (38–62) | 6 (2–15) |
OR (95% CI) | 4.3 (2.2–8.4) | 13.8 (4.6–41.9) | 15 (4.9–45.9) | |||
Abbreviation: OR=odds ratio.
aORR defined as the best confirmed overall response (CR or PR).
bCBR defined as CR or PR or SD ≥6 months.
In the SG safety population (n=258), rates of treatment-emergent AEs (TEAEs) that led to SG discontinuation or death were low and were similar among BMI subgroups. The rates of the most common (≥10%) Grade ≥3 TEAEs (neutropenia, diarrhea, leukopenia, infections and infestations, anemia, and febrile neutropenia) were higher in the obese subgroup than in the underweight/normal subgroup. In the obese subgroup, diarrhea and infection led to SG discontinuation in 1 patient each; no patients in the obese subgroup discontinued SG due to neutropenia, leukopenia, anemia, or febrile neutropenia.
References
1. TRODELVY® Gilead Sciences Inc. Trodelvy (sacituzumab govitecan-hziy) for injection, for intravenous use. U.S. Prescribing Information. Foster City, CA.
Abbreviations
Page 1 of 7
AE=adverse event
BICR=blinded independent central review
BMNeg=negative for brain metastasis
BMPos=positive for brain metastasis
CBR=clinical benefit rate
CR=complete response
DOR=duration of response
HR=hazard ratio
mTNBC=metastatic triple-negative breast cancer
ORR=objective response rate
OS=overall survival
PFS=progression-free survival
PR=partial response
SD=stable disease
SG=sacituzumab govitecan-hziy
TPC=treatment of physician’s choice
TRAE=treatment-related adverse event
Product Label
For the full indication, important safety information, and boxed warning(s), please refer to the Trodelvy US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.
Follow-Up
For any additional questions, please contact Trodelvy Medical Information at:
☎1‐888-983-4668 or www.askgileadmedical.com
Adverse Event Reporting
Please report all adverse events to:
Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
www.gilead.com/utility/contact/report-an-adverse-event
FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or www.accessdata.fda.gov/scripts/medwatch
Data Privacy
The Medical Information service at Gilead Sciences may collect, store, and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.
It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers, and regulatory authorities located in countries other than your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact privacy@gilead.com.
TRODELVY, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2024 Gilead Sciences, Inc.
Page 1 of 7