Use of sacituzumab govitecan safe, efficacious in pretreated metastatic breast cancer

A recent China study has provided further evidence on the real-world efficacy and safety of sacituzumab govitecan (SG) in HR+/HER2- and triple-negative breast cancer (TNBC) patients who have received at least three lines of prior therapy.

“SG demonstrates robust clinically meaningful efficacy and a manageable safety profile in heavily pretreated patients with HER2- metastatic breast cancer (mBC),” said lead study author Dr Xu Liang, Department of Breast Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing, China.

Liang and colleagues obtained retrospective data from three hospitals on HER2- mBC patients who received SG treatment between June 2023 and December 2024 and had completed at least one imaging assessment. They assessed the following outcomes: real-world progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), real-world overall survival (OS), and safety.

Fifty-eight HER2- mBC patients (median age 52.5 years) treated with SG were included in this real-world multicentre study. They had received a median of three prior lines of therapy in the metastatic setting. SG was administered as second-line treatment in 31 percent of patients and as third- or later-line in 69 percent. [SABCS 2025, abstract 603]

Of the participants, 43 (74.1 percent) had TNBC and 15 (25.9 percent) HR+/HER2-, with metastases found in the liver (55.2 percent), bone (53.3 percent), lung (41.4 percent), and brain (20.6 percent).

Efficacy outcomes

The ORR in the overall population was 34.5 percent over a median follow-up of 11.0 months, with a DCR of 81.0 percent. The median OS was 16.32 months, and the 6-month OS rate was 77.6 percent, while the median PFS was 4.41 months.

The ORR in metastatic TNBC patients was 34.8 percent, and the DCR was 79.1 percent. The median PFS in this population was 4.97 months, while the median OS was 16.32 months. Among HR+/HER2- patients who received a median of two lines of prior endocrine therapy and chemotherapy, the ORR was 33.33 percent, DCR was 86.6 percent, median PFS was 4.41 months, and median OS was not reached.

Twelve patients had brain metastases at baseline (11 TNBC and one HR+/HER2- BC), including three with stable brain metastases without prior radiotherapy, five with stable brain metastases post-radiotherapy, and four with newly diagnosed active brain metastases without radiotherapy. Their ORR was 25 percent, DCR was 91.6 percent, median PFS was 5.43 months, and median OS was 17.50 months.

Furthermore, the intracranial ORR was 41.6 percent, and the median intracranial PFS was 14.9 months. Two patients underwent concurrent chemoradiotherapy, with one achieving intracranial complete response and the other partial response. Both remained free of intracranial progression and had PFS of >14.9 months.

“SG showed robust disease control in both subgroups, notably in patients with brain metastases, who showed better outcomes than the overall population, suggesting potential blood-brain barrier permeability of SG,” Liang said. “This provides a new therapeutic option for patients with brain metastases lacking effective treatments.”

Safety profile

The most common adverse events were neutropenia (51.7 percent) and diarrhoea (22.4 percent), with grade ≥3 incidences of 15.5 percent and 6.9 percent, respectively. A few patients (1.7 percent) experienced febrile neutropenia.

Moreover, 36.2 percent of patients received prophylactic granulocyte colony-stimulating factor (G-CSF), and 15.5 percent received long-acting G-CSF as primary prophylaxis, none of whom had grade ≥3 neutropenia.

“Compared with global trials, lower incidences of neutropenia and diarrhoea were observed, possibly reflecting improved supportive care, especially that prophylactic G-CSF use clinically reduced the incidence and severity of SG-related neutropenia,” Liang said.

“Future studies should explore SG plus local therapies for brain metastases and standardized G-CSF prophylaxis to optimize outcomes,” Liang added.