Sacituzumab Govitecan Maintains QOL Benefit Over Chemotherapy in Previously Untreated TNBC

Treatment with sacituzumab govitecan-hziy (Trodelvy) led to meaningful and sustained quality of life (QOL) benefit for patients with previously untreated advanced triple-negative breast cancer (TNBC) despite an increase in gastrointestinal (GI) toxicities with the regimen vs chemotherapy, according to patient-reported outcome (PRO) data from the phase 3 ASCENT-03 trial (NCT05382299) presented during the 2025 San Antonio Breast Cancer Symposium.¹

Physical functioning scores from baseline to week 25 were maintained with sacituzumab govitecan, while a continuous trend towards deterioration was observed over time with chemotherapy. Among patients who underwent a PRO assessment at week 25, the mean change from baseline (CFB) in physical functioning scores with sacituzumab govitecan (n = 158) was 1.1 (SD, 18.32) vs –6.2 (SD, 16.77) with chemotherapy (n = 135). The median CFBs at week 25 were 0 and –6.7, respectively. Furthermore, the least square mean difference between physical functioning scores at week 25 was 6.9 (SE, 1.72) and favored sacituzumab govitecan over chemotherapy (95% CI, 3.50-10.28).

Moreover, the TTD in fatigue was comparable between treatment groups, and consistent over 2 consecutive visits. The median TTD was 1.4 months (95% CI, 1.1-1.7) in the sacituzumab arm (n = 279) vs 1.6 months (95% CI, 1.2-1.9) in the chemotherapy arm (stratified HR, 0.98; 95% CI, 0.80-1.19). The time to confirmed deterioration (TTCD) in the respective arms was 1.5 months (95% CI, 1.1-2.1) and 1.9 months (95% CI, 1.2-2.7), for a stratified HR of 0.96 (95% CI, 0.78-1.18).

“These data complement the clinically meaningful progression-free survival [PFS] benefit that has been observed with sacituzumab govitecan over chemotherapy in this setting, and do support sacituzuma govitecan as a potential new standard of care for patients with previously untreated metastatic TNBC who were not candidates for immune checkpoint inhibition,” Kevin Punie, MD, a medical oncologist at the Oncological Center Antwerp in Ziekenhuis Aan de Stroom, Antwerp, Belgium, stated in his presentation of the data.

What is the design of ASCENT-03?

ASCENT-03 is a randomized, open-label trial enrolling patients with previously untreated, locally advanced, inoperable or metastatic TNBC who were not candidates for PD-L1 inhibition and were at least 6 months out since treatment in the curative setting.^1,2 Other key eligibility factors included measurable disease per RECIST 1.1 criteria, and ECOG performance status of 0 or 1, and adequate organ function. Patients with previously treated, stable central nervous system metastases are permitted to enroll. Stratification factors include location (United States/Canada/Western Europe vs the rest of the world) and whether patients had de novo metastatic TNBC, recurrent disease within 6 to 12 months of treatment or recurrent disease after at least 12 months from treatment in the curative setting.¹

A total of 558 patients were randomly assigned 1:1 to the sacituzumab govitecan or chemotherapy arm (n = 279 each).¹ In the experimental arm, sacituzumab govitecan was administered intravenously at a dose of 10 mg/kg on days 1 and 8 of a 21-day cycle. In the chemotherapy arm, patients received 90 mg/m² of paclitaxel; 100 mg/m² of nab-paclitaxel on days 1, 8 and 15 of a 28-day cycle; or 1000 mg/m² of gemcitabine plus carboplatin at AUC2 on days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as verified by blinded independent central review (BICR), or unacceptable toxicity. Of note, eligible patients were allowed to cross over to receive sacituzumab govitecan in the second line following verified disease progression.

The study’s primary end point is PFS by BICR; key secondary end points are overall survival, overall response rate, duration of response, time to response by BICR, safety and QOL. Additional QOL end points are being evaluated.

How was this PRO analysis conducted?

The QOL comprised both the key secondary end points of CFB in physical functioning at week 25 and TTD in fatigue; as well as exploratory end points of CFB at week 25 (excluding physical functioning), TTD (excluding fatigue), TTCD, and time to first improvement (TTI).

PROs were assessed using the EORTC QLC-C30 questionnaire and were evaluated at baseline at the start of each treatment cycle until the end of the visit. More than 80% of patients in both arms completed the PRO questionnaires up to week 25. At baseline, week 13, and week 25, the completion rates in the sacituzumab govitecan arm were 98%, 86%, and 85%, respectively. Corresponding completion rates in the chemotherapy arm were 98%, 88%, and 82%.

“Baseline domain scores were quite similar and balanced between the treatment groups,” Punie noted. “When baseline PRO data were compared with data from the larger patient population, it was clear that some domains, like physical functioning, role functioning and pain clearly tended to have worse baseline scores."

How did CFB, TTD, and TTI differ by functional and symptom domains with sacituzumab govitecan vs chemotherapy?

Exploratory analyses showed that CFB in role functioning, (difference, 5.33; 95% CI, 3.60-13.06; minimum important difference [MD], 8.24), global health status/QOL (4.41; 95% CI, 0.58-8.24; 6.44), fatigue (–5.89; 95% CI, –10.43 to –1.36; 7.12), pain (–6.18; 95% CI, –11.20 to –1.16; 8.52) and dyspnea (–5.11; 95% CI, –9.83 to –0.36; 7.24) all favored sacituzumab govitecan over chemotherapy. CFB for diarrhea did favor chemotherapy over sacituzumab govitecan (5.52; 95% CI, 0.84-10.20; 4.24). However, investigators noted that GI-related toxicities with sacituzumab govitecan were consistent with the agent’s known safety profile and were manageable according to standard guidelines.

TTD was similar across functioning and symptom domains in both arms, but favored sacituzumab govitecanover chemotherapy for dyspnea (HR, 0.69; 95% CI, 0.54-0.87); physical (HR, 0.88; 95% CI, 0.70-1.10), role (HR, 1.05; 95% CI, 0.85-1.29), and social functioning (HR, 1.05; 95% CI, 0.85-1.30); and fatigue (HR, 0.98; 95% CI, 0.80-1.19) and insomnia (HR, 0.89; 95% CI, 0.70-1.12). Conversely, TTD for diarrhea (HR, 1.98; 95% CI, 1.58-2.48) and nausea/vomiting (HR, 1.44; 95% CI, 1.16-1.78) was worsened with sacitizumab govitecan vs chemotherapy.

Of note, TTI was shorter with sacituzumab govitecan vs chemotherapy in domains with over 50% of patients eligible for improvement. These included physical (HR, 1.70; 95% CI, 1.23-2.34), role (HR, 1.47; 95% CI, 1.10-1.97), and social functioning (HR, 1.30; 95% CI, 0.99-1.71), as well as fatigue (HR, 1.43; 95% CI, 1.11-1.84) and insomnia (HR, 1.44; 95% CI, 1.12-1.85).
Disclosures: Punie serves as a consultant for AstraZeneca, Axiom, Eli Lilly, Exact Sciences, Focus Patient, Gilead Sciences, Hoffmann/La Roche, Medscape, MSD, Mundi Pharma, Need Inc., NordicPharma, Novartis, Pfizer; Sanofi, Seagen; and has received a grant/research support from Novartis.

References

1. Punie K, Tolaney S, Huvitz S, et al. Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) vs chemotherapy in patients with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors in the phase 3 ASCENT-03 study. Presented at: 2025 San Antonio Breast Conference Symposium; December 9-12, 2024; San Antonio, TX. RF6-05.
2. Study of sacituzumab govitecan-hziy versus treatment of physician's choice in patients with previously untreated locally advanced inoperable or metastatic triple-negative breast cancer (ASCENT-03). ClinicalTrials.gov. Updated September 5, 2025. Accessed December 10, 2025. https://clinicaltrials.gov/study/NCT05382299