Sacituzumab govitecan in metastatic triple-negative breast cancer patients treated at Institut Curie Hospitals: efficacy, safety, and impact of brain metastases

Abstract

Background Sacituzumab govitecan (SG) has been approved by FDA in April 2021 for pre-treated metastatic triple-negative breast cancer (mTNBC), following the ASCENT trial results. Methods We set up an ambispective bicentric cohort study to assess the real-world effectiveness and safety of SG in patients with mTNBC treated at Institut Curie Hospitals, with a focus on patients with brain metastases. Results This study included 99 patients treated through the French Early Access Program to SG from May 2021 to January 2023. Median age was 55 years [26–89], N = 8 patients (8%) had BRCA1/2 mutation, N = 12 (12%) de novo stage IV disease and N = 31 (31%) brain metastases. Patients had previously received a median of two [1–10] lines of treatment in advanced setting. After a median follow-up of 9.7 months, the median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95%CI[3.4–5.0]) and 8.6 months (95%CI[7.1–11.9]), respectively, while objective response rate was 29% (95%CI[21–39]). Among patients with brain metastases, median PFS and OS were 3.7 months (95%CI[2.6–6.2]) and 6.7 months (95%CI[6.3–NR]), respectively, with intracranial tumor responses. Dose reductions were required in N = 17 patients (17%) within a median of three [2–11] cycles, due to gastrointestinal toxicity (N = 6; 6%), hematological toxicity (N = 9; 9%) including febrile neutropenia (N = 2; 2%), liver enzyme elevation (N = 1; 1%), and physical deterioration (N = 1; 1%). There was no related death to SG. Conclusions The observed response rate and safety of SG are consistent with the results of the ASCENT trial, with efficacy observed in patients with brain metastases, but observed PFS and OS are numerically shorter.

Real-world use patterns, effectiveness, and tolerability of sacituzumab govitecan for second-line and later-line treatment of metastatic triple-negative breast cancer in the United States

“…There are a few reports in the published literature of SG use in real-world studies in patients with mTNBC. Data from "real-world" French, British, German, Italian, and United States studies have reported outcomes for patients treated with SG in 2L and later lines [15,[17][18][19][20]. Similar to the current study, patients in these real-world studies tended to have poorer performance status and a higher proportion of patients had visceral metastases and central nervous system disease compared with those in the clinical trials [15,[17][18][19][20].…”

“…Data from "real-world" French, British, German, Italian, and United States studies have reported outcomes for patients treated with SG in 2L and later lines [15,[17][18][19][20]. Similar to the current study, patients in these real-world studies tended to have poorer performance status and a higher proportion of patients had visceral metastases and central nervous system disease compared with those in the clinical trials [15,[17][18][19][20]. In the current analysis, 111 patients were previously treated with a PD-(L)1 inhibitor in the metastatic setting while only 22 had PD-L1 positive results; this may be the result of missingness in the database (70% of patients had an unknown PD-L1 expression status); alternatively, patients may have been positive for microsatellite instability-high and tumor mutational burden-high as pembrolizumab is a preferred treatment for these patients [12].…”

“…It is important to determine how SG is being utilized in real-world settings and to identify optimal treatment approaches for health care professionals. Due to the recent approval, there are few studies of SG use in patients with mTNBC in the real-world setting [15][16][17][18][19][20]. The objective of this study was to describe patient characteristics, treatment patterns, tolerability, and clinical outcomes in patients with mTNBC who received at least one dose of SG in the 2L and later-line setting in clinical practices in the United States.…”