A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple‐negative breast cancer who received at least two prior treatments

Abstract

Refractory or relapsing metastatic triple‐negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody‐drug conjugate, targeting human trophoblast cell‐surface antigen 2 (Trop‐2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER‐132‐001 (NCT04454437) was a multicenter, single‐arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21‐day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression‐free survival (PFS), overall survival (OS) and safety. Eighty female Chinese patients (median age 47.6 years; range 24‐69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0‐8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06‐50.30) and 43.8% (95% CI, 32.68‐55.30) of patients, respectively. The median PFS was 5.55 months (95% CI, 4.14‐N/A). SG‐related Grade ≥3 treatment‐emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%) and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pretreated Chinese patients with mTNBC. The observed safety profile was generally manageable.

Postmarketing Safety of Sacituzumab Govitecan: A Pharmacovigilance Study Based on the FDA Adverse Event Reporting System

“…A single‐arm multicenter study reported one patient who died from shock during the third treatment cycle. Prior to the onset of shock, this patient experienced sacituzumab govitecan–related diarrhea and bone marrow suppression, which led to severe and refractory diarrhea‐induced hypovolemia, shock, and multiorgan failure, considered as a potential contributing factor to the fatal outcome 4 . Therefore, healthcare professionals should advise patients to seek medical attention immediately if diarrhea occurs to prevent irreversible body harm.…”

“…1,2 The particular subtype, triple-negative breast cancer (TNBC), regarded as the most aggressive form, constitutes ~ 15% of all BC occurrences. 3,4 TNBC is characterized by low expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and progesterone receptor (PR). Thus, TNBC is insensitive to hormone therapies and epidermal growth factor receptor (EGFR) antagonists, necessitating chemotherapy as the principal therapeutic intervention.…”

“…More alarmingly, some severe adverse effects (SAEs) have the potential to result in fatality. 4,19 It could be inferred that sacituzumab govitecan might instigate serious AEs that are yet to be identified. Therefore, the systematic examination of adverse event incidence, especially severe ones, is paramount to ensure the safety of patients undergoing medication.…”

“…Breast cancer (BC) remains a primary contributor to mortality in women, accounting for 11.7% of all cancer cases 1,2 . The particular subtype, triple‐negative breast cancer (TNBC), regarded as the most aggressive form, constitutes ~ 15% of all BC occurrences 3,4 . TNBC is characterized by low expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and progesterone receptor (PR).…”

“…Certain investigations have highlighted that patients may exhibit symptoms such as fatigue, dyspnea, and hyperglycemia. More alarmingly, some severe adverse effects (SAEs) have the potential to result in fatality 4,19 . It could be inferred that sacituzumab govitecan might instigate serious AEs that are yet to be identified.…”