Sacituzumab Govitecan for the treatment of advanced triple negative breast cancer patients: a multi-center real-world analysis

Abstract

ObjectiveThe objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy.MethodsData were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER <1%), progesterone receptor (PgR <1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria. Demographic and clinical characteristics were collected. Premedication, dose modifications and treatment schedule were based on the approved label of the product. Adverse events (AEs) were assessed according to NCI-CTCAE v5.0.ResultsFifty-seven eligible patients who received sacituzumab govitecan for mTNBC were included. Median age was 53 years (range 25-75). Approximately 70% of patients had an initial diagnosis of TNBC. Median time from the diagnosis of metastatic BC to start of sacituzumab govitecan was 17 months (range 0-97) and median number of previous therapies was 3 (range 1-7). The most common sites of metastasis were lymph nodes (63.1% of patients), lung (57.9%), bone (50.8%) and liver (38.6%). Eight (14.0%) patients had a disease-free interval ≤12 months. A total of 32 (56.1%) deaths were observed and the median overall survival (OS) was 12.43 months (95% CI, 7.97 months-not reached). At a median follow-up of 10.6 months, 45 patients (78.9%) had progression and the median progression-free survival (PFS) was 4.9 months (95% CI, 3.7-7.1 months). Partial tumour response was observed in 19 patients (33.3%), stable disease in 16 (28.1%) and disease progression in 22 patients (38.6%). The most common treatment-related AEs were anemia (66.6% of patients), alopecia (66.6%), neutropenia (59.6%), nausea (42.1%) and diarrhea (38.6%). Neutropenia was the most common serious treatment-related AE: 21.0% and 8.7% of patients experienced grade 3 or 4 neutropenia, respectively. Twenty-two patients (38.6%) reduced the dose and 5.3% permanently discontinued treatment.ConclusionThe results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.

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.…”

Effects of Garlic on Breast Tumor Cells with a Triple Negative Phenotype: Peculiar Subtype-Dependent Down-Modulation of Akt Signaling

“…The management of TNBCs primarily includes surgical removal, radiotherapy, and/or chemotherapy, often resulting in side effects and in drug resistance, which diminish the therapeutic potential of many interventions. Despite the wide range of novel treatment approaches currently under investigation, including PARP inhibitors, immune-checkpoint inhibitors, and antibody-drug conjugates (ADCs), additional investigations are necessary to identify TNBC patients who could most benefit from them [13][14][15]. Therefore, it is currently of great interest to identify new strategies adjuvating conventional therapies, and there is increasing consideration of the use of natural substances, due to their potent biological activities and mild side effects [16].…”

Impact of khat (Catha edulis) and oral contraceptive use on telomerase levels and tumor suppressor genes p53 and p21 in normal subjects and breast cancer patients

“…Despite major advancements in its early diagnosis and treatment, conventional therapeutic strategies have shown limitations in effectively treating BC. However, the advent of antibody–drug conjugates, a new class of drug designed to specifically deliver high-potent chemotherapeutic agents directly to cancer cells, has made a breakthrough in the treatment of BC patients 10 – 12 .…”