First-line sacituzumab govitecan ups PFS in metastatic TBNC

First-line treatment with sacituzumab govitecan, an antibody drug conjugate, significantly improved progression-free survival (PFS) compared with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC), according to the ASCENT-03 trial presented at ESMO 2025.

The ASCENT-03 trial met its primary endpoint, with sacituzumab govitecan demonstrating a statistically significant and clinically meaningful improvement in PFS, as assessed by a blinded independent central review (BICR), compared with standard chemotherapy, said Dr Javier Cortés from the International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain.

This global, open-label, phase III trial included 558 patients with previously untreated, locally advanced, unresectable or metastatic TNBC who were randomized in a 1:1 ratio to receive either sacituzumab govitecan* or chemotherapy** (n=279 in each arm).

PFS per BICR, investigator

At a median follow-up of 13.2 months, patients treated with sacituzumab govitecan had a significantly longer median PFS per BICR than those treated with chemotherapy (9.7 vs 6.9 months), which resulted in a 38-percent reduction in the risk of disease progression or death (hazard ratio [HR], 0.62; p<0.0001). [ESMO 2025, abstract LBA20]

Similarly, the investigator-assessed PFS also favoured sacituzumab govitecan over chemotherapy, with a median PFS of 9.6 vs 6.8 months (HR, 0.64).

The 6- and 12-month PFS rates were higher among patients treated with sacituzumab govitecan compared with chemotherapy, as shown by BICR (65 percent vs 53 percent and 41 percent vs 24 percent, respectively) and investigator (65 percent vs 52 percent and 38 percent vs 22 percent) assessments.

Furthermore, the PFS benefit observed with sacituzumab govitecan was consistent across all prespecified subgroups, including age, ECOG PS, geographic region, disease status, PD-L1 status, and chemotherapy prior to randomization, Cortés noted.

Secondary endpoints

The objective response rate was similar between the sacituzumab govitecan and chemotherapy arms (48 percent vs 46 percent), but the median duration of response was longer with sacituzumab govitecan (12.2 vs 7.2 months).

Overall survival (OS) data was still immature at the time of the primary analysis, with comparable OS rates in both treatment arms (21.5 [sacituzumab govitecan] and 20.2 [chemotherapy] months).

Safety endpoints

Both sacituzumab govitecan and chemotherapy arms had similar rates of grade ≥3 (66 percent vs 62 percent) and serious (26 percent and 24 percent) treatment-emergent adverse events (TEAEs), but fewer patients discontinued treatment due to AEs in the sacituzumab govitecan arm (4.1 percent vs 13.5 percent).

The most common grade ≥3 TEAEs reported with sacituzumab govitecan were neutropenia (43 percent) and diarrhoea (9 percent), while neutropenia (41 percent) and anaemia (16 percent) were reported with chemotherapy.

“The AEs observed were consistent with the known safety profile of sacituzumab govitecan,” noted Cortés.

New first-line standard of care?

“Almost half of the patients diagnosed with metastatic TNBC do not receive treatment beyond first-line, demonstrating an urgent need for innovative treatment options in this early setting,” Cortés said in a press release.

“In this trial, sacituzumab govitecan as a first-line treatment resulted in longer survival than chemotherapy in patients with metastatic TNBC who were not candidates for a PD-1 or PD-L1 inhibitor; without sacituzumab govitecan as an option, many such patients may not survive to receive further treatment,” the researchers noted in a published paper. [N Engl J Med 2024;doi:10.1056/NEJMoa2511734]

“This data might support a potential new standard, a potential good option for patients with TNBC when they develop metastasis and are unable to receive immune checkpoint inhibitors,” Cortés said.