Sacituzumab Govitecan Upholds Efficacy and Safety in Real-World mTNBC Population

Efficacy and safety outcomes with sacituzumab govitecan-hziy (Trodelvy) in real-world patients with metastatic triple-negative breast cancer (mTNBC) who received the agent in the second- or later-line setting were similar to those observed in prior clinical trials and real-world studies, according to findings from a retrospective analysis.1

The data, which were presented at the 42nd Annual Miami Breast Cancer Conference, showed that at a median follow-up of 10.0 months (range, 0.6-51.3), the median real-world overall survival (OS) among patients who received sacituzumab govitecan in the second-line or later setting (n = 409) was 11.3 months (95% CI, 10.0-12.8). The 12- and 24-month OS rates were 47.5% (95% CI, 42.4%-52.4%) and 22.5% (95% CI, 17.8%-27.5%), respectively.

The median real-world progression-free survival (PFS) was 5.0 months (95% CI, 4.4-5.5). The 3- and 6-month PFS rates were 66.8% (95% CI, 62%-71.2%) and 42.4% (95% CI, 37.5%-47.2%), respectively.

Regarding safety, in the overall study population, based on manual chart abstraction of structured laboratory results, 68.7% of patients had neutropenia, and the median time from sacituzumab govitecan initiation to neutropenia onset was 8 days. Additionally, 60.4% of patients used granulocyte colony–stimulating factor during sacituzumab govitecan treatment as primary prophylaxis (21.5%), secondary prophylaxis (27.4%), and only as treatment for neutropenia (11.5%). Overall, the most common adverse effects (AEs) collected through manual curation were fatigue (47.4%), diarrhea (38.1%), neutropenia (34.7%), and nausea (32.0%).

“Safety and efficacy are consistent with previous findings, even in this racially diverse real-world population with more patients at higher ECOG performance status compared to pivotal clinical trials,” lead study author Vikram C. Gorantla, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania, and coauthors wrote in a poster presentation of the data.

Sacituzumab Govitecan’s Place in the TNBC Treatment Paradigm

Sacituzumab govitecan is a TROP2-directed antibody-drug conjugate (ADC) that was granted accelerated approval by the FDA in April 2020 for the treatment of adult patients with mTNBC who had received at least 2 prior lines of therapy for metastatic disease.2 In April 2021, the FDA granted regular approval to the agent for the treatment of patients with unresectable, locally advanced or metastatic disease who have received at least 2 prior lines of systemic therapy, including at least 1 line of therapy in the metastatic setting.3

In the confirmatory phase 3 ASCENT trial (NCT02574455), patients with previously treated mTNBC who received sacituzumab govitecan achieved a median PFS of 4.8 months (95% CI, 4.1-5.8) vs 1.7 months (95% CI, 1.5-2.5) with single-agent chemotherapy (HR, 0.43; 95% CI, 0.35-0.54; P < .0001). The median OS in these respective arms was 11.8 months (95% CI, 10.5-13.8) and 6.9 months (95% CI, 5.9-7.6; HR, 0.51 [95% CI, 0.41-0.62; P < .0001). Sacituzumab govitecan was also associated with a manageable safety profile in this trial. The most common grade 3 or higher AEs were neutropenia, leukopenia, diarrhea, anemia, and febrile neutropenia.

This real-world study described the demographics, clinical characteristics, treatment patterns, and treatment outcomes for real-world patients with mTNBC who received sacituzumab govitecan in the second line or later.1

“The present study builds on findings of recent observational studies and is designed to include longer follow-up to further characterize early adoption and real-world utilization patterns of sacituzumab govitecan for treatment of mTNBC,” the authors noted.

Real-World Study Methods and Design

This retrospective, observational study used the Integra Connect Precision-Q de-identified database, which has real-world electronic health record data from more than 3.2 million patients and more than 5000 providers across community oncology clinics in the United States (US). This database consists of manually curated, structured patient-level data, such as diagnosis codes, comorbidities, laboratory values, treatment dose, treatment duration. The database also includes unstructured fields, such as physician notes, reasons for treatment discontinuation, biomarker testing information, response details, medical events, and disease progression information.

This real-world study included data from adult patients diagnosed with mTNBC who were treated at US community oncology sites and received sacituzumab govitecan in the second line or later between April 1, 2020, and December 31, 2023. Patients were excluded if they had a diagnosis of any other primary cancer or if they participated in a clinical trial during the study observation period.

Patient Characteristics

In the total study population, the median age at sacituzumab govitecan initiation was 61 years (range, 28-89), and 99.3% of patients were female. Patients were White (69.2%), Black/African American (16.9%), Asian (2.7%), or of unknown race (11.2%). This population included patients from the southern (61.6%), northeastern (22.0%), midwestern (10.0%), and western (6.4%) regions of the US. Patients’ ECOG performance statuses included 0 or 1 (69.9%), 2 or higher (13.2%), and unknown (16.9%). In total, 23.2% of patients had de novo metastatic disease. Patients had metastases in visceral regions (lung or liver; 73.4%), bone (52.8%), and brain (21.3%). A total of 28.9% of patients had HER2-low disease at the time of mTNBC diagnosis. BRCA statuses in the study population included wild-type (82.4%), variant (9.0%), and unknown/untested (8.6%). PD-L1 statuses in the study population were positive (defined as a combined positive score [CPS] of ≥ 10; 27.6%), negative (defined as a CPS of < 10; 60.1%), and unknown/untested (12.2%).

Patients received sacituzumab govitecan as their second (46.9%), third (31.3%), and fourth or later (21.8%) line of treatment; 5.1% of patients received the ADC in multiple lines of treatment.

Real-World Sacituzumab Govitecan Treatment Patterns

Most patients (59.9%) received chemotherapy prior to initiating sacituzumab govitecan in the second- or later-line setting. Patients had a median sacituzumab govitecan starting dose across lines of treatment. The median starting dose was 10 mg/kg (range, 4.1-11.4), and patients received a median of 10 doses (range, 1-135).

In total, 43.1% of patients had dose reductions. Investigators did not observe appreciable differences in dose reduction rates when stratified by lines of treatment.

Overall, 65.0% of patients had dose delays, defined as any delay in sacituzumab govitecan treatment that lasted at least 7 days. The median time from sacituzumab govitecan initiation to the first dose delay event (defined as 1 day after the last administration prior to the delay) was 13.5 days (range, 1-682). Patients with dose delays had their first delay in cycle 1 (51.9%), cycle 2 (11.3%), cycle 3 (9%), and cycle 4 or later (27.8%).

The median time to treatment discontinuation or death was 3.9 months (95% CI, 3.5-4.6). The median time to next treatment or death was 6.0 months (95% CI, 5.3-6.6).

References

1. Gorantla V, Choski R, Kudrik F, et al. Real-world sacituzumab govitecan treatment patterns and outcomes in second-line or later metastatic triple negative breast cancer: leveraging electronic health records and manual curation of a US database. Presented at: 42nd Annual Miami Breast Cancer Conference. March 6-9, 2025; Miami, Florida. Poster 31.
2. FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer. FDA. April 22, 2020. Accessed March 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer
3. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. Updated April 8, 2021. Accessed March 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer