在转移性三阴性乳腺癌患者中 sacituzumab govitecan 与化疗对比的 III 期 ASCENT 研究中的生物标志物分析。

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

机构信息

Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.

出版信息

Ann Oncol. 2021 Sep;32(9):1148-1156. doi: 10.1016/j.annonc.2021.06.002. Epub 2021 Jun 8.

DOI:10.1016/j.annonc.2021.06.002

PMID:34116144

Abstract

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 high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations.

CONCLUSIONS

SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.

摘要

背景

关键性 III 期 ASCENT 试验表明，与单药化疗（TPC）相比，抗滋养层细胞表面抗原 2（抗 Trop-2）抗体药物偶联物 sacituzumab govitecan（SG）可改善先前治疗的转移性三阴性乳腺癌（mTNBC）患者的生存结局，该药物与拓扑异构酶抑制剂 SN-38 相连。这项来自 ASCENT 试验的预设探索性生物标志物分析评估了肿瘤 Trop-2 表达与种系 BRCA1/2 突变状态与临床结局之间的关系。

患者和方法

先前接受过两种或两种以上化疗且进展或不耐受的 mTNBC 患者，或在转移环境中接受过一次或多次化疗的患者，被随机分配接受 SG（静脉注射 10mg/kg，第 1 天和第 8 天，每 21 天一次）或 TPC（卡培他滨、艾立布林、长春瑞滨或吉西他滨），直至疾病进展/无法耐受毒性。在研究入组时采集活检或手术标本，使用经过验证的免疫组织化学检测和组织化学评分来确定 Trop-2 表达水平。在基线时收集种系 BRCA1/2 突变状态。

结果

在可评估的 468 例患者中，290 例有 Trop-2 表达数据[64%（n=151 SG）与 60%（n=139 TPC）]，292 例有已知 BRCA1/2 突变状态[63%（n=149 SG）与 61%（n=143 TPC）]。SG 治疗与 TPC 治疗患者的中位无进展生存期分别为 6.9、5.6 和 2.7 个月，高、中、低 Trop-2 表达患者的中位总生存期分别为 14.2、14.9 和 9.3 个月。高、中、低 Trop-2 表达患者的客观缓解率分别为 44%、38%和 22%，SG 治疗患者的中位总生存期分别为 14.2、14.9 和 9.3 个月，与 TPC 治疗患者的 6.9、6.9 和 7.6 个月相比，分别为 44%、38%和 22%，SG 治疗患者的中位总生存期分别为 14.2、14.9 和 9.3 个月，与 TPC 治疗患者的 6.9、6.9 和 7.6 个月相比，分别为 44%、38%和 22%。SG 治疗与 TPC 治疗在高、中、低 Trop-2 表达患者中的疗效结局均优于 TPC 治疗。无论种系 BRCA1/2 突变状态如何，SG 治疗与 TPC 治疗相比，均能使患者获益。