Trodelvy® (sacituzumab govitecan-hziy)

Use in Older Patients With mBC

This document is in response to your request for information regarding the use of Trodelvy® (sacituzumab govitecan-hziy [SG]) in older patients (defined as ≥65 years of age) with metastatic breast cancer (mBC).

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.

• Of the 366 patients with TNBC who were treated with SG, 19% of patients were ≥65 years and 3% were ≥75 years. Patients ≥65 had an increased incidence of neutropenia, including fatal outcomes. No other differences in safety and effectiveness were observed between patients ≥65 years of age and younger patients.

SG is indicated for the treatment of adult patients with unresectable locally advanced or metastatic HR+, HER2- (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and ≥2 additional systemic therapies in the metastatic setting.

• Of the 322 patients with HR+/HER2- breast cancer who were treated with SG, 26% of patients were ≥65 years and 6% were ≥75 years. No overall differences in effectiveness were observed between patients ≥65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged ≥65 years (14%) compared with younger patients (3%).

SG Clinical Data in Older Patients With mBC

Post hoc subgroup analyses of patients ≥65 y treated with SG in ASCENT (a mTNBC study)2 and TROPiCS-02 (a HR+/HER2- mBC study)3 reported generally similar mPFS and mOS vs the ITT population. Regardless of age, mPFS and mOS numerically favored SG vs TPC.4-6

• ASCENT: mPFS for SG and TPC, respectively, was 7.1 and 2.4 mo in patients ≥65 y, 4.2 and 1.6 mo in patients <65 y, and 4.8 and 1.7 mo in the ITT population. mOS for SG and TPC, respectively was 14.7 and 8.9 mo in patients ≥65 y, 10.8 and 6.7 mo in patients <65 y, and 11.8 and 6.9 mo in the ITT population.2,6

• TROPiCS-02: mPFS for SG and TPC, respectively, was 6.7 and 3.5 mo in patients ≥65 y, 5.5 and 4.1 mo in patients <65 y, and 5.5 and 4 mo in the ITT population. mPFS in patients ≥65 y with an SG RDI >90% was 6.7 mo vs 5.5 mo for SG RDIs ≤74% and >74 to ≤90%. mOS in the SG and TPC arms, respectively was 14.9 and 10.1 mo in patients ≥65 y, 14.1 and 11.5 mo in patients <65 y, and 14.4 and 11.2 mo in the ITT population.3,5,7

In ASCENT, older patients in the SG arm had a slightly higher rate of Grade ≥3 TEAEs vs TPC (69 vs 63%). Patients ≥65 y experienced higher rates of TEAEs that led to dose reduction vs patients <65 y (37 vs 19%). The incidence of TEAEs leading to SG treatment discontinuation was 2% in older patients and 5% in the OSP and patients <65 y.6

• In older patients treated with SG vs TPC, the most common Grade ≥3 TEAEs were neutropenia (47 vs 40%) and anemia (14 vs 6%). Grade ≥3 diarrhea was reported by 12% of patients receiving SG, there were no reported cases with TPC.6,8

In TROPiCS-02, older patients in the SG arm reported more TEAEs that led to dose reduction and treatment discontinuation vs TPC, and TEAEs within the older SG subgroup led to dose reduction and treatment discontinuation more commonly vs the <65 y subgroup. Rates of Grade ≥3 TEAEs and TEAEs that led to treatment interruptions were similar across age subgroups but occurred at higher rates in patients treated with SG vs TPC.5

• In older patients treated with SG vs TPC, the most common Grade ≥3 TEAEs were neutropenia (44 vs 36%) and diarrhea (17 vs 2%).

SG Clinical Data in Older Patients With mBC

ASCENT Study in mTNBC

An open‑label, randomized, phase 3 study (N=529), investigated the efficacy and safety of SG 10 mg/kg IV on Days 1 and 8 of a 21-day cycle vs TPC in patients with refractory or relapsed mTNBC who had received ≥2 prior chemotherapies for unresectable, locally advanced, or metastatic disease. The primary outcome was mPFS in patients without brain metastasis. In the ITT population, mPFS was 4.8 vs 1.7 mo (HR 0.43; 95% CI 0.35–0.54), and mOS was 11.8 vs 6.9 mo (HR 0.51; 95% CI 0.41–0.62) with SG and TPC, respectively.2

Post Hoc Subgroup Analysis in Patients <65 and ≥65 Years

Approximately 19% of patients were ≥65 y, of these, 8 and 13 patients in the SG and TPC arms respectively, were ≥75 y. Most older patients vs patients <65 y were female (99 vs >99%) and White (85 vs 78%).6,9 See Table 1 for select baseline demographics and characteristics.

Table 1. ASCENT: Select Baseline Demographics and Characteristics6

aRefers to any prior metastatic/neoadjuvant/locally advanced regimens used to treat an eligible breast cancer patient. Prior therapy in the adjuvant setting is excluded from this count.

In general, disease characteristics were similar between patients <65 y and ≥65 y with some exceptions. Patients <65 y with known BRCA 1/2 status had a higher rate (61%) of negative germline BRCA mutations vs patients ≥65 y (35%). Generally, the most common prior regimens were used at higher frequencies in patients <65 vs ≥65 y, including anthracyclines (86 vs 67%, respectively) and cyclophosphamide (85 vs 73%), prior checkpoint inhibitors (30 vs 23%), and neoadjuvant systemic therapies (53 vs 24%).6

Efficacy results6

SG improved outcomes vs TPC in older patients. See Table 2 for outcomes by age.

Table 2. ASCENT: Efficacy in Patients <65 and ≥65 Years6

Safety results

Within the OSP, patients who received ≥1 dose of study drug (n=482), older patients in the SG arm had a slightly higher rate of Grade ≥3 TEAEs vs TPC. Patients ≥65 y were more likely to undergo dose reduction due to TEAEs vs patients <65 y. The incidence of TEAEs leading to SG treatment discontinuation was 2% in older patients and 5% in the OSP. See Table 3 for further TEAEs in the OSP and in patients <65 and ≥65 y.6

Table 3. ASCENT: Safety Summary of the OSP and Patients <65 and ≥65 Years6

In the OSP, the most common any grade TEAEs, in both treatment arms, included diarrhea (65%), neutropenia (64%), nausea (62%), and fatigue (52%). These were the most common any grade TEAEs in older patients; all occurred at a higher frequency with SG than TPC. The most common Grade ≥3 TEAEs for SG in the OSP were neutropenia (52%) and diarrhea (11%); these were the most common Grade ≥3 TEAEs in patients ≥65 y and occurred at a higher frequency than with TPC (Table 4).6

Table 4. ASCENT: TEAEs in the OSP and in Patients <65 and ≥65 Years8,10

Abbreviations: NR=not reported.

a TEAEs occurring in ≥30% of patients in either treatment arm within either age subgroup.

b Grade ≥3 adverse event not reported in ≥5% of patients in the SG arm or TPC arm.

c Any grade adverse event not reported in ≥20% of patients in the SG arm or TPC arm.

TROPiCS-02 Study in HR+/HER2- mBC

An open-label, randomized, multicenter phase 3 study, investigated the efficacy and safety of SG 10 mg/kg IV on Days 1 and 8 of a 21-day cycle vs TPC in patients with HR+/HER2- mBC who were previously treated with ≥1 taxane, ≥1 endocrine therapy, and ≥1 CDK4/6i in any setting, and who had received ≥2 and ≤4 prior chemotherapy regimens for metastatic disease. Patients received SG (n=272) or single-agent TPC (eribulin, vinorelbine, gemcitabine, capecitabine [n=271]).3

In the ITT population, mPFS was 5.5 (4.2–7) vs 4 (3.1–4.4) mo (HR, 0.66; 95% CI 0.53–0.83; P=0.0003)3 and mOS was 14.4 (13–15.7) vs 11.2 (10.1–12.7) mo (HR, 0.79; 95% CI 0.65–0.96; P=0.02) for SG and TPC, respectively.7

Post Hoc Subgroup analysis

Safety and efficacy was assessed in patients <65 vs ≥65 y5 and <75 vs ≥75 y4; ≈26% (n=140) were ≥65 y, of those, 24 were ≥75 y. Most older patients were female (SG, 100%; TPC, 99%) and White (SG, 68%; TPC, 64% [race was not reported in 41 older patients]). Baseline characteristics were generally similar across treatments. A higher proportion of patients had an ECOG PS of 1 vs 0 in the ≥65 vs <65 y (Table 5) and the ≥75 vs <75 y subgroups, respectively.4,5

Table 5. TROPiCS-02: Select Demographics and Baseline Characteristics in Patients <65 and ≥65 Years5

aUse was unknown in 7 patients <65 y and in 1 patient ≥65 y.

Efficacy results

Regardless of age, mPFS (by BICR) and mOS numerically favored SG vs TPC (Table 6).4,5

Table 6. TROPiCS-02: Efficacy According to Age Subgroup4,5

aPer BICR. bRefers to patients <65 and ≥65 y. cRefers to patients <75 and ≥75 y.

mPFS was numerically higher in older patients with an RDI (cumulative SG dose divided by total planned SG dose) of >90% vs ≤74% and >74 to ≤90% (Table 7).5

Table 7. TROPiCS-02: Efficacy by RDI in Patients <65 and ≥65 Years5

SG had a longer TTD for fatigue in patients <65 y (Table 8) vs TPC. SG was also numerically favored vs TPC for median TTD for global health status/QoL in patients <65 and ≥65 y, and for median TTD for pain in patients ≥65 y.5

Table 8. TROPiCS-02: TTD of QoL in Patients <65 and ≥65 Years5

Safety results

Patients ≥65 y treated with SG, experienced more TEAEs that led to dose reduction and treatment discontinuation vs patients ≥65 y treated with TPC. TEAEs in the SG arm that led to dose reduction and treatment discontinuation were more common in patients ≥65 vs those <65 y. Grade ≥3 TEAEs and TEAEs that led to treatment interruptions occurred at higher rates in patients treated with SG vs TPC, and the rates of these TEAEs were similar across age subgroups (Table 9 and Table 10).5 In the ≥75 y subgroup, Grade ≥3 TEAEs were more common vs other subgroups, as were TEAEs that led to dose reductions, however, the small sample size for this subgroup limits interpretation.4

Table 9. TROPiCS-02: TEAEs According to Age Subgroup4,5

Table 10. TROPiCS-02: Most Common TEAEs in Patients <65 and ≥65 Years5

TEAEs occurring in ≥30% of patients in either treatment arm within either age subgroup.

1. TRODELVY® Gilead Sciences Inc. Trodelvy (sacituzumab govitecan-hziy) for injection, for intravenous use. U.S. Prescribing Information. Foster City, CA.

2. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541.

3. Rugo HS, Bardia A, Marme F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022;40(29):3365-3376.

4. Bardia A, Schmid P, Tolaney S, et al. Efficacy and clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer [Abstract 1578376]. Presented at: San Antonio Breast Cancer symposium (SABCS); December 5-9, 2023; San Antonio, TX.

5. Bardia A, Schmid P, Tolaney S, et al. Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer [Poster PO5-21-09]. Presented at: San Antonio Breast Cancer symposium (SABCS); December 5-9, 2023; San Antonio, TX.

6. Hurvitz SA, Bardia A, Punie K, et al. Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer. 2024;10(1):33.

7. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023;S0140-6736(23):01245-X.

8. Hurvitz SA, Bardia A, Punie K, et al. Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer [Supplementary Appendix]. NPJ Breast Cancer. 2024;10(1):33.

9. Rugo HS, Tolaney SM, Loirat D, et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer. 2022;98(8).

10. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer [Supplementary Appendix]. N Engl J Med. 2021;384(16):1529-1541.

BICR=blinded independent central review
BRCA=breast cancer gene
CDK4/6i=cyclin-dependent kinase 4/6 inhibitor
ECOG PS=Eastern Cooperative Oncology Group performance status
HR=hazard ratio
HR+/HER2-=hormone receptor-positive/human epidermal growth factor receptor 2-negative
mBC=metastatic breast cancer
mOS=median overall survival
mPFS=median progression-free survival
mTNBC=metastatic triple-negative breast cancer
NE=not estimable
NR=not reported
ORR=objective response rate
OSP=overall safety population
QoL=quality of life
RDI=relative dose intensity
SG-hziy=sacituzumab govitecan
TEAE=treatment-emergent adverse event
TPC=treatment of physician’s choice
TTD=time to deterioration
 

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.
© 2025 Gilead Sciences, Inc.