Trodelvy Shows Fewer Side Effects Than Chemotherapy in Some With TNBC

Treatment with Trodelvy (sacituzumab govitecan-hziy) elicited fewer side effects that led to dose reduction or stopping treatment altogether compared with chemotherapy in patients with previously untreated triple-negative breast cancer (TNBC). According to a detailed safety analysis presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), side effects like neutropenia and diarrhea, resolved quickly with standard treatment.

The findings showed that nearly all patients experienced treatment-emergent side effects: 99% of those who received the antibody-drug conjugate (ADC; 275 patients) versus 97% of those given chemotherapy (276 patients). Of the seven treatment-emergent side effects that proved fatal, six were caused by infections related to treatment. Five infections were linked to neutropenia in patients at risk for febrile neutropenia who did not receive granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis.

The median time to onset of diarrhea was shorter for those who received the ADC compared with chemotherapy. The median duration of diarrhea was similar between the ADC and chemotherapy groups. Neutropenia showed comparable timing, though both side effects were most frequent early in treatment with Trodelvy.

“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, and colleagues, wrote in a poster.

The study enrolled patients with previously untreated locally advanced unresectable or metastatic TNBC. Tumors were either PD-L1 negative, defined as a combined positive score (CPS) below 10, or PD-L1 positive, defined as a CPS of 10 or higher, with prior exposure to PD-(L)1 inhibition in the (neo)adjuvant setting or a comorbidity preventing that therapy.

Participants were randomly assigned to receive the ADC intravenously at 10 mg/kg on days 1 and 8 of 21-day treatment cycles or chemotherapy in the form of paclitaxel, nab-paclitaxel (Abraxane), or gemcitabine paired with carboplatin. Treatment continued until disease progression or intolerable toxicity.

The primary end point was progression-free survival assessed by blinded independent central review. Key secondary end points included overall survival, objective response rate, duration of response, and safety.

Earlier results showed median progression-free survival with Trodelvy was 9.7 months versus 6.9 months with chemotherapy. The objective response rate was 48% versus 46%, and median duration of response was 12.2 months versus 7.2 months, respectively.

The current safety analysis reported the first in-depth review of side effects, examining incidence, severity, time to onset, duration, and impact of management.

Demographics were well balanced between treatment arms. The median patient age was 55.5 years. Nearly all patients were female, more than half were White, most had an ECOG performance status of 0, and the majority were PD-L1 negative. Most patients were from Europe and Asia/Pacific.

Median treatment duration for Trodelvy was 8.3 months compared with 5.8 months for carboplatin, 6.1 months for gemcitabine, and 6.3 months for taxanes. Exposure-adjusted incidence rates for grade 3 or higher side effects favored Trodelvy compared with chemotherapy, as did serious side effects and treatment-emergent side effects leading to dose interruption, reduction, or treatment discontinuation.

Trodelvy showed lower rates of neutropenia, febrile neutropenia, anemia, thrombocytopenia, diarrhea, fatigue, and peripheral neuropathy compared with chemotherapy.

Primary prophylaxis with G-CSF was associated with less frequent and severe neutropenia in the Trodelvy arm. Of the 54 patients receiving G-CSF with the ADC, 52% experienced any-grade neutropenia and 28% experienced grade 3 or higher neutropenia. In the chemotherapy arm, 28 patients receiving G-CSF had rates of 75% and 50%, respectively.

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 Dr. 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 Javier Cortés. The New England Journal of Medicine.