Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer

作者：Aditya Bardia, Sara M. Tolaney, Kevin Punie, Delphine Loirat, Mafalda Oliveira, Kevin Kalinsky, Amelia Zelnak, Philippe Aftimos, Florence Dalenc, Sagar Sardesai, Erika Hamilton, Priyanka Sharma, Sabela Recalde, Eva Ciruelos Gil, T Traina, Joyce O’Shaughnessy, Javier Cortés, Mu‐Hung Tsai, Linda T. Vahdat, Véronique Dièras, Lisa A. Carey, Hope S. Rugo, David M. Goldenberg, Q. Hong, Martin Olivo, Loretta M. Itri, Sara A. Hurvitz · 发表于：Annals of Oncology · 年份：2021 · DOI：10.1016/j.annonc.2021.06.002 · 被引用次数：318 · 研究领域：HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies、Breast Cancer Treatment Studies

BACKGROUND: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. PATIENTS AND METHODS: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. RESULTS: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for h...