Sacituzumab Govitecan/Pembro Maintains QOL, Physical Functioning in mTNBC

Sacituzumab govitecan (Trodelvy) in combination with pembrolizumab (Keytruda) was associated with maintained quality of life (QOL) in patients with previously untreated PD-L1–positive metastatic triple-negative breast cancer (mTNBC) according to patient-reported outcomes (PROs) from the phase 3 ASCENT-04/KEYNOTE-D19 study (NCT05382286).

Further, the analysis, presented at the 2025 ESMO Annual Congress, showed the combination may potentially provide a delay in the onset of physical decline.

“[Sacituzumab govitecan] plus pembrolizumab maintained overall QOL,” Evandro de Azambuja, MD, PhD, head of the Medical Support Team at the Jules Bordet Institute, Brussels, Belgium, said during a presentation of the data. “Patients reported reduced symptom burden and improved functioning in multiple domains. These data complement the clinically meaningful improvement in progression-free survival [PFS]³ and support this treatment regimen as a potential new standard of care for patients with PD-L1–positive mTNBC.”

Did the combination of sacituzumab govitecan plus pembrolizumab improve symptom burden?

In the presentation, time to first meaningful deterioration or death (TTD)–defined as meaningful within-patient change (MWPC) from baseline of 13.33 points or greater for physical functioning and 10 points or more for other domains–and least squares mean (LSM) change from baseline in EORTC QLQ-C30 domains in the intent-to-treat population were reported.

TTD in physical functioning was comparable between the sacituzumab govitecan plus pembrolizumab and chemotherapy plus pembrolizumab groups (median, 3.0 months [95% CI, 2.3-4.6] vs 3.5 months [95% CI, 2.9-4.2], respectively; HR, 0.95; 95% CI, 0.73-1.22).

However, the sensitivity analysis showed prolonged time to first deterioration with sacituzumab govitecan regimen compared with chemotherapy (median, 9.3 months [95% CI, 6.1-not estimable] vs 6.9 months [95% CI, 5.6-8.3], respectively; HR, 0.82; 95% CI, 0.60-1.11). Time to confirmed deterioration through the sensitivity analysis also showed a prolonged duration of 8.8 months (95% CI, 5.1-13.1) with sacituzumab govitecan plus pembrolizumab vs 5.7 months (95% CI, 4.4-7.0) with pembrolizumab plus chemotherapy (HR, 0.84; 95% CI, 0.62-1.12).

“Both sensitivity analyses consistently showed that sacituzumab govitecan plus pembrolizumab has a numerically longer time to deterioration and may delay the onset of decline in physical functioning,” de Azambuja said. “If you look into different domains, quality of life was maintained across different domains.”

According to TTD in EORTC QLQ-C30 domains, emotional functioning (median, 9.3 months [95% CI, 5.9-NE] vs 4.9 [95% CI, 3.5-6.3], respectively) and pain (median, 4.3 [95% CI, 2.4-5.7] vs 3.2 [95% CI, 2.2-4.2]) were favored with sacituzumab govitecan plus pembrolizumab compared with pembrolizumab plus chemotherapy.

“There was worsening of symptoms such as nausea/vomiting and diarrhea, which are consistent with the safety profile of the sacituzumab govitecan plus pembrolizumab group in the study, and can be managed by following established guidelines,” de Azambuja said.

Lastly, from baseline to EORTC QLQ-C30 scores, the sacituzumab govitecan regimen was more favorable compared with the chemotherapy regimen for physical (LSM change, 2.45; 95% CI, 0.09-4.81), role (LSM change, 3.34; 95% CI, 0.13-6.55), and emotional (LSM change, 4.07; 95% CI, 1.20-6.93) functioning, as well as pain (LSM change, -5.39; 95% CI, -8.55 to -2.23) and insomnia (LSM change, -4.59; 95% CI, -7.70 to -1.48).

What are the unmet needs in frontline mTNBC treatment?

According to de Azambuja, approximately 50% of patients with mTNBC who receive first-line treatment do not receive second-line therapy, which includes a substantial deterioration in QOL with each line of therapy. He added that frontline therapy may be an important opportunity to control disease without worsening QOL.

“Patient-reported outcome will provide insight from impact on treatments, including symptom burden and functional status,” de Azambuja said.

The investigators evaluated QOL as a secondary end point of the trial, including TTD in physical functioning, and TTD in the role of functioning GHS/QOL, pain, and fatigue.

PRO assessments occurred at baseline, day 1 of all cycles, and the end of treatment. Questionnaires were completed in about 70% of treatment arms, de Azambuja noted.

Baseline EORTC QLQ-C30 domain scores were consistent between treatment groups and with general population scores for most domains.

Did sacituzumab govitecan plus pembrolizumab Improve PFS in PD-L1–positive mTNBC?

The randomized, open-label, phase 3 ASCENT-04/KEYNOTE-D19 trial evaluated the efficacy of sacituzumab govitecan in combination with pembrolizumab vs pembrolizumab plus physician’s choice of chemotherapy in patients with previously untreated, locally advanced, inoperable or metastatic TNBC whose tumors expressed PD-L1 with a CPS of 10 or greater.² Four hundred and forty-three patients were randomized 1:1 to receive either sacituzumab govitecan plus pembrolizumab (n = 221) or pembrolizumab plus chemotherapy (n = 222).

The sacituzumab govitecan regimen reduce the risk for disease progression by 35% (HR, 0.65; 95% CI, 0.51-0.84; P = .0009) after a median follow-up of 14 months.³ Further, median duration of response was 16.5 for sacituzumab govitecan plus pembrolizumab compared with 9.2 months with pembrolizumab plus chemotherapy.

Of note, the most frequent grade 3 or higher treatment-emergent adverse events (TEAEs) with the sacituzumab govitecan regimen were neutropenia (43%) and diarrhea (10%) and with the chemotherapy regimen were neutropenia (45%), anemia (16%), and thrombocytopenia (14%).

“The primary analysis of ASCENT-04 showed a statistically significant and clinically important improvement in median progressive-free survival with [sacituzumab govitecan] plus pembrolizumab as first-line treatment for untreated PD-L1–positive metastatic triple-negative breast cancer,” de Azambuja said.

References

1. De Azambuja E, Schmid P, Kalinsky KM, et al. Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in patients (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) in the phase III ASCENT-04/KEYNOTE-D19 study. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA22.
2. OncLive. Sacituzumab Govitecan Plus Pembrolizumab Improves PFS in PD-L1–Positive mTNBC. Published: April 21, 2025. Accessed: October 20, 2025. https://www.onclive.com/view/sacituzumab-govitecan-plus-pembrolizumab-improves-pfs-in-pd-l1-positive-mtnbc
3. Tolaney S, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(suppl 17):abstract LBA109. doi: 10.1200/JCO.2025.43.17_suppl.LBA109.