Treatment with Trodelvy (Sacituzumab govitecan) reduced the risk for disease progression or death by 38% versus chemotherapy among patients with previously untreated, locally advanced, unresectable, or metastatic triple-negative breast cancer (TNBC) not eligible for PD-1 or PD-L1 inhibitors, according to data from the phase 3 ASCENT-03 trial presented at the 2025 ESMO Congress.
In addition to improvements in progression-free survival (PFS), Trodelvy achieved a superior duration of response (DOR) with no new safety signals.
“This data may support a potential new standard and a good option for patients with metastatic TNBC who cannot receive immune checkpoint inhibitors,” said Dr. Javier C. Cortés, head of the International Breast Cancer Centre in Barcelona, Spain.
Efficacy of Trodelvy in mTNBC
Among patients treated with Trodelvy, median PFS was 9.7 months versus 6.9 months with chemotherapy. PFS rates were higher with Trodelvy compared with chemotherapy at 6 months (65% versus 53%) and 12 months (41% versus 24%). Investigator-assessed PFS was 9.6 months with Trodelvy versus 6.8 months with chemotherapy. Six- and 12-month PFS rates were 65% and 52% with Trodelvy versus 38% and 22% with chemotherapy.
PFS benefit was observed across all subgroups, including by age, ECOG performance status, geographic region, disease state, PD-L1 status, and prior chemotherapy. Objective response rate (ORR) was 48% with Trodelvy versus 46% with chemotherapy. Complete response occurred in 20 patients (7%) versus 15 patients (5%), partial response in 115 (41%) versus 112 (40%), stable disease in 113 (41%) versus 101 (36%), and progressive disease in 14 (5%) versus 36 (13%).
“Objective response rates were similar; however, duration of response was substantially longer with Trodelvy,” Cortés noted. Median DOR was 12.2 months versus 7.2 months with chemotherapy. Time to response was 1.6 months in both groups.
Overall survival (OS) data were not mature at presentation. Among 179 patients who initiated subsequent treatment after chemotherapy, 147 (82%) received Trodelvy. Median OS was 21.5 months versus 20.2 months. Median PFS2 was 18.2 months versus 14.0 months.
Side Effects of Trodelvy During the ASCENT-03 Trial
Median treatment duration with Trodelvy was 8.3 months. Treatment-emergent side effects occurred in 99% versus 97% of patients, with grade 3 or higher side effects in 66% versus 62% and treatment-related events in 61% versus 53%.
There were 71 serious side effects in the Trodelvy arm, 46 treatment related. Side effects led to treatment discontinuation in 10 patients, dose interruptions in 181, and dose reductions in 101. Seven side effects led to death, mostly infections, including five secondary to neutropenia. None of the five patients at risk for febrile neutropenia received prophylaxis with G-CSF.
Most common grade 3 or higher side effects included neutropenia (43%), diarrhea (9%), and leukopenia (7%). Side effects leading to discontinuation occurred in 4% versus 12%.
Unmet Needs in Advanced TNBC
“Chemotherapy has been the mainstay for metastatic TNBC, and absolute improvements in median OS have been modest,” said Dr. Ana C. Garrido-Castro, Dana-Farber Cancer Institute and Harvard Medical School.
“Approximately 25% to 30% of patients with metastatic TNBC do not survive 6 months from diagnosis, roughly the median PFS of first-line chemotherapy. A new drug that significantly improves PFS with acceptable toxicity should change the first-line standard of care.”
Most patients with previously untreated metastatic TNBC are not candidates for PD-1 or PD-L1 inhibitors. About half do not receive a second-line therapy. “The majority will experience progressive disease and need subsequent therapies. Improved options in earlier lines are urgently needed,” Cortés added.
ASCENT-03 Trial Design
Trodelvy is approved for metastatic TNBC in the second line and beyond and for pre-treated HR-positive/HER2-negative metastatic breast cancer globally.
In ASCENT-03, patients with previously untreated, locally advanced, unresectable, or metastatic TNBC not eligible for immune checkpoint therapy were randomized 1:1 to receive intravenous (IV) Trodelvy on days 1 and 8 of 21-day cycles (279 patients) or chemotherapy (279 patients).
Treatment continued until progression or unacceptable toxicity. Eligible patients could cross over to second-line Trodelvy after progression. Patients were eligible if not candidates for PD-1 or PD-L1 inhibitors and were 6 months or less since curative treatment. Previously treated stable central nervous system metastases were allowed. PFS by served as the primary end point. Secondary end points included OS, ORR, DOR, time to response, safety, and quality of life.
Median age was 56 versus 54. Most patients were White (64% each), ECOG 0 (66% vs 67%), PD-L1 negative (99% each), had lung metastases (59% vs 61%), received prior neoadjuvant therapy (66% vs 68%), and 48% had recurrence ≥12 months after curative treatment.
References:
- "Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)." by Dr. Javier C. Cortés, et al. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin Germany. Abstract LBA20.
- "Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer," Dr. Javier C. Cortés. New England Journal of Medicine.
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