TNBC | Image Credit: ©
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Sacituzumab govitecan-hziy (Trodelvy) was safe and effective for the treatment of patients with metastatic triple-negative breast cancer (TNBC), according to findings from a retrospective real-world study presented during the 42nd Annual Miami Breast Cancer Conference.1
Findings showed that at the December 31, 2023, data cutoff and a median follow-up of 8.7 months (IQR, 4.5-14.6), real-world patients who received sacituzumab govitecan in the second line or later (n = 381) achieved a median overall survival (OS) of 11.3 months (95% CI, 10.0-12.9). The 12- and 24-month OS rates were 47% (95% CI, 41%-52%) and 19% (95% CI, 14%-25%), respectively.
Grade 2 neutropenia occurred in 25% of patients during sacituzumab govitecan treatment; 27% of patients experienced grade 3/4 neutropenia during therapy. Most patients (59%) received concomitantgranulocyte colony-stimulating factor (G-CSF); the median time from the initiation of sacituzumab govitecan to the first administration of G-CSF was 12 days (IQR, 8-30). Grade 2 and grade 3/4 neutropenia occurred at rates of 13% and 10%, respectively, among patients who received any G-CSF prophylaxis (n = 117). These respective rates were 28% and 13% in patients who received no G-CSF (n = 156). Grade 2 and grade 3/4 neutropenia were both reported at rates of 4% among patients who received primary G-CSF prophylaxis only (n = 77).
“There is a need for physicians to understand the management of neutropenia and effectiveness of sacituzumab govitecan in the real world,” Rita Nanda, MD, and coauthors wrote in a poster presentation of the results. “The incidence of grade 2 and grade 3/4 neutropenia was low among patients receiving G-CSF prophylaxis, suggesting that sacituzumab govitecan–related neutropenia can be effectively managed with prophylactic G-CSF use.”
Nanda is the director of the Breast Oncology Program and an associate professor of medicine at University of Chicago Medicine in Illinois.
In April 2021, sacituzumab govitecan received regular approval from the FDA for the treatment of patients with unresectable locally advanced or metastatic TNBC following 2 or more prior systemic therapies, including at least 1 for metastatic disease.2 The regulatory decision was supported by findings from the phase 3 ASCENT trial (NCT02574455), which demonstrated that patients who received sacituzumab govitecan (n = 267) achieved a median progression-free survival of 4.8 months (95% CI, 4.1-5.8) compared with 1.7 months (95% CI, 1.5-2.5) among those who received chemotherapy (n = 262; HR, 0.43; 95% CI, 0.35-0.54; P < .0001). The median OS was 11.8 months (95% CI, 10.5-13.8) vs 6.9 months (95% CI, 5.9-7.6), respectively (HR, 0.51; 95% CI, 0.41-0.62; P < .0001).
Real-World Study Design and Baseline Patient Characteristics
The retrospective, observational cohort study employed the nationwide longitudinal Flatiron Health deidentified database, which contains electronic health record–derived patient-level data from approximately 280 United States cancer clinics.1 Investigators included data from adult patients with metastatic TNBC treated with sacituzumab govitecan in the second line or later from April 2020 through June 2023. Patients with evidence of other primary tumors—with the exception of nonmetastatic nonmelanoma skin cancers—within 5 years prior to their diagnosis of metastatic breast cancer were excluded from the analysis.
The objective of the analysis was to evaluate the incidence and management of neutropenia and clinical outcomes of patients with metastatic TNBC receiving sacituzumab govitecan as a second line or later.
At baseline, the median age in the overall population was 61 years (IQR, 52-69). Most patients were female (99%), White (61%), were treated in a community setting (78%), had an ECOG performance status of 0 or 1 (65%), had recurrent disease (66%), and had HER2-negative (immunohistochemistry 0) disease (64%). The median time from early breast cancer diagnosis to metastatic breast cancer was 30 months (IQR, 17-55). Twenty-three percent of patients had brain metastases.
Prior therapies included taxanes (62%), PD-(L)1 inhibitors (44%), and PARP inhibitors (7%). Patients included in the analysis received sacituzumab govitecan in the second line (n = 118) or the third line and beyond (n = 263).
Data regarding sacituzumab govitecan use patterns revealed that patients received a median of 12 total doses (IQR, 5-21) of the agent. The maximum number of doses given during the study period was 74. The median treatment duration was 4.0 months (IQR, 1.9-7.6); the median duration among patients treated in the second line or the third line and beyond was 4.2 months (IQR, 1.6-8.1) and 4.0 months (IQR, 2.1-7.4), respectively.
The median relative dose intensity was 90% (IQR, 71%-102%). Most patients (76%) had a relative dose intensity above 70%, and 24% had a relative dose intensity below 70%. Fifty-five percent of patients received a subsequent line of therapy following sacituzumab govitecan, and the median number of lines of treatment given after sacituzumab govitecan was 2 (IQR, 1-2). Thirteen percent of patients were still receiving sacituzumab govitecan at the data cutoff.
TTNTD Data and Additional Safety Findings
Additional efficacy data showed that the median time to next treatment or death (TTNTD) was 5.6 months (95% CI, 5.0-6.4). The 3- and 6-month TTNTD rates were 75% (95% CI, 71%-80%) and 48% (95% CI, 43%-53%), respectively.
Sacituzumab govitecan dose reductions occurred at a rate of 44% among patients with available dosing data (n = 308).
Grade 2 or grade 3/4 neutropenia was reported in patients who received secondary G-CSF prophylaxis at rates of 19% and 31%, respectively. These respective rates were 33% and 17% for those who received therapeutic G-CSF only (n = 24).
“In this real-world study, sacituzumab govitecan demonstrated effectiveness and a manageable safety profile in patients treated in [the] second line or later for metastatic TNBC, consistent with results from the phase 3 ASCENT study and other real-world evidence studies,” the study authors wrote in conclusion.
References
Nanda R, Yam C, Spring L, et al. Management of neutropenia and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer treated in real-world settings in the United States. Presented at: 42nd Annual Miami Breast Cancer Conference. March 6-9, 2024; Miami, Florida.
FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. April 8, 2021. Accessed March 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer