Trodelvy Shows Fewer Severe Side Effects vs Chemo in Untreated TNBC

A safety analysis of the phase 3 ASCENT-03 study showed that among patients with previously untreated triple-negative breast cancer (TNBC) who were treated with Trodelvy (sacituzumab govitecan-hziy) experienced fewer side effects that required dose reductions or stopping treatment compared with those receiving chemotherapy. Common side effects, including neutropenia and diarrhea, were quickly managed and resolved with standard care.

In the study, presented at the 2025 San Antonio Breast Cancer Symposium, nearly all patients experienced some side effects, with 99% of those receiving Trodelvy and 97% receiving chemotherapy reporting at least one event. Fatal side effects were rare, and most were related to infections, particularly in patients at risk for febrile neutropenia who did not receive preventive treatment with growth factors.

Diarrhea appeared sooner in patients on Trodelvy than chemotherapy, but the duration of diarrhea was similar between groups. Neutropenia followed a similar pattern, with side effects most common early in treatment.

“These results support Trodelvy as an effective treatment with manageable side effects for people with metastatic triple-negative breast cancer who are not candidates for PD-L1–targeting therapy,” Dr. Sara A. Hurvitz, of UW Medicine and Fred Hutchinson Cancer Center, explained in the presentation.

How was the ASCENT-03 Trial Conducted?

The ASCENT-03 trial enrolled patients with previously untreated, locally advanced unresectable or metastatic TNBC. Participants were either PD-L1 negative or had previously received PD-(L)1 inhibitors or had other health reasons preventing PD-(L)1 therapy.

Patients were randomly assigned to Trodelvy intravenously on days 1 and 8 of a 21-day cycle or chemotherapy, including paclitaxel, Abraxane, or gemcitabine with carboplatin. Treatment continued until disease progression or intolerable side effects.

The main goal was to measure progression-free survival. Secondary goals included overall survival, response rate, duration of response, and safety.

Prior Efficacy Findings from ASCENT-03

Earlier results showed that Trodelvy improved progression-free survival to 9.7 months versus 6.9 months with chemotherapy. Response rates were also higher, with 48% achieving a response versus 46% with chemotherapy, and responses lasted longer on Trodelvy.

Highlights From the Latest Safety Analysis of ASCENT-03

The new analysis looked at side effects in detail, including how often they occurred, severity, timing, duration, and how well they could be managed. Patients’ ages ranged from 23 to 86, most were female, more than half were White, and most had good performance status. Treatment lasted a median of 8.3 months for Trodelvy versus around 6 months for chemotherapy.

Trodelvy was associated with fewer severe side effects than chemotherapy. Dose interruptions, dose reductions, and treatment discontinuations were all less common with Trodelvy.

Trodelvy-related neutropenia was less frequent and severe in patients receiving preventive growth factor therapy. Of those who received it, 52% experienced any neutropenia and 28% experienced severe neutropenia. Among patients on chemotherapy who received preventive therapy, these rates were higher at 75% and 50%, respectively.

Overall, the study shows that Trodelvy can be an effective frontline option for patients with triple-negative breast cancer, with side effects that are generally manageable and resolve with standard interventions.

References

1. “Safety analysis of ASCENT-03, a phase 3 study of sacituzumab govitecan vs chemotherapy for previously untreated advanced triple-negative breast cancer in patients who are not candidates for PD-(L)1 inhibitors,” by Sara A. Hurvitz. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; Houston, TX. Poster PS1-13-24.
2. “Sacituzumab govitecan in untreated, advanced triple-negative breast cancer,” by Dr. Javier Cortés. The New England Journal of Medicine.

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