Effectiveness of sacituzumab govitecan and management of neutropenia in patients with metastatic triple-negative breast cancer treated in real-world settings in the United States

Abstract

Background: Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, demonstrated efficacy and manageable safety in second-line or later (2L+) metastatic triple-negative breast cancer (mTNBC) in clinical trials. We describe the real-world effectiveness of SG as 2L+ mTNBC treatment and the proportion of patients with neutropenia and its management.

Patients and methods: This study used a nationwide electronic health record-derived de-identified database. Patients with mTNBC receiving SG in 2L+ from April 2020 through June 2023 were included. Real-world overall survival (rwOS) and time to next treatment or death (TTNTD) were assessed using the Kaplan-Meier method. SG use patterns, rates of neutropenia, and granulocyte colony-stimulating factor (G-CSF) use were described.

Results: For 381 patients included in the analysis, the median [interquartile range (IQR)] age was 61 years (52-69 years); 17% (n = 66) had ECOG PS ≥2; 18% (n = 70) were black; 78% (n = 298) were treated in community settings. Patients received a median (IQR) of 2 (1-3) prior treatment lines for metastatic disease. Median (IQR) SG treatment duration was 4.0 months (1.9-7.6 months) (maximum 32.7 months). At a median (IQR) follow-up of 8.7 months (4.5-14.6 months), the median rwOS and TTNTD were 11.3 months [95% confidence (CI) 10.0-12.9 months] and 5.6 months (95% CI 5.0-6.4 months), respectively. Grade 2 and 3/4 neutropenia during SG treatment occurred in 25% (n = 94) and 27% (n = 101) of patients, respectively. Any G-CSF use (primary + secondary prophylaxis and/or treatment) was observed in 59% (n = 225) of patients; 31% (n = 117) received any G-CSF prophylaxis. Any-grade neutropenia occurred in 25% (n = 29) of patients receiving any G-CSF prophylaxis versus 44% (n = 68) of patients who did not receive G-CSF.

Conclusions: SG demonstrated real-world effectiveness and manageable safety, consistent with findings from ASCENT and other published real-world studies. Patients receiving any G-CSF prophylaxis had low rates of any-grade neutropenia, suggesting SG-related neutropenia can be effectively managed with G-CSF in patients with increased risk for febrile neutropenia.

Keywords: G-CSF use; effectiveness; neutropenia; real-world clinical outcomes; sacituzumab govitecan; triple-negative breast cancer.

Figure 1

Kaplan–Meier analysis. Real--world overall survival (A) and time to next treatment or death (B) for patients with mTNBC receiving SG in 2L or later. 2L, second line; CI, confidence interval; mTNBC, metastatic triple-negative breast cancer; rwOS, real-world overall survival; SG, sacituzumab govitecan; TTNTD, time to next treatment or death.

Figure 2

Subgroup analysis of survival outcomes in patients with mTNBC receiving SG in 2L+. 2L+ second line or later; 3L+, third line or later; CI, confidence interval; eBC, early breast cancer; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; mBC, metastatic breast cancer; mTNBC, metastatic triple-negative breast cancer; rwOS, real-world overall survival; SG, sacituzumab govitecan; TTNTD, time to next treatment or death.

Figure 3

G-CSF use and management of neutropenia. Five patients received G-CSF during SG treatment, but usage was not categorized as prophylactic or therapeutic. Four patients received both primary and secondary prophylaxis. Neutropenic events were defined using the International Classification of Diseases (ICD) 10/9 diagnostic codes (D70, 288) and/or laboratory data (absolute neutrophil count <1500 mm³). G-CSF, granulocyte colony-stimulating factor; IQR, interquartile range; N/A, not applicable; NP, neutropenia; SG, sacituzumab govitecan. ^aFor patients receiving primary or secondary prophylaxis, onset date refers to NP after G-CSF use. ^bNP after G-CSF use. ^cRefers to grade ≥2 NP.