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

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.

• Authors: A Bardia, S M Tolaney, K Punie, D Loirat, M Oliveira, K Kalinsky, A Zelnak, P Aftimos, F Dalenc, S Sardesai, E Hamilton, P Sharma, S Recalde, E C Gil, T Traina, J O'Shaughnessy, J Cortes, M Tsai, L Vahdat, V Diéras, L A Carey, H S Rugo, D M Goldenberg, Q Hong, M Olivo, L M Itri, S A Hurvitz
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 32 Issue 9 Pg. 1148-1156 (09 2021) ISSN: 1569-8041 [Electronic] England
• PMID: 34116144 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Immunoconjugates
• sacituzumab govitecan
• Camptothecin

Topics

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Camptothecin (analogs & derivatives)
• Humans
• Immunoconjugates
• Triple Negative Breast Neoplasms (drug therapy, genetics)