Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression
Year: 2024
Type: article
Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Sacituzumab govitecan (SG), a first-in-class anti–trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physician's choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study. Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression. Final efficacy secondary end point analyses and post hoc analyses of outcomes stratified by Trop-2 expression and human epidermal growth factor receptor 2 status are reported. Updated safety analyses are provided. In this final analysis, SG (n = 267) improved median progression-free survival (PFS; 4.8 v 1.7 months; hazard ratio (HR), 0.41 [95% CI, 0.33 to 0.52]) and median overall survival (OS; 11.8 v 6.9 months; HR, 0.51 [95% CI, 0.42 to 0.63]) over TPC (n = 262). SG improved PFS over TPC in each Trop-2 expression quartile (n = 168); a trend was observed for improved OS across quartiles. Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups. These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.23.01409
Authors: Aditya Bardia, Hope S. Rugo, Sara M. Tolaney, Delphine Loirat, Kevin Punie, Mafalda Oliveira, Adam Brufsky, Kevin Kalinsky, Javier Cortés, Joyce O' Shaughnessy, Véronique Diéras, Lisa A. Carey, Luca Gianni, Martine Piccart-Gebhart, Sibylle Loibl, Oh Kyu Yoon, Yang Pan, Scott Hofsess, See-Chun Phan, Sara A. Hurvitz
Institutions: Harvard University, Massachusetts General Hospital, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Dana-Farber Cancer Institute, Institut Curie, Universitair Ziekenhuis Leuven, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Magee-Womens Hospital, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Emory University, Winship Cancer Institute, Baylor University Medical Center, Centre Eugène Marquis, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Université Libre de Bruxelles, Institut Jules Bordet, Gilead Sciences (United States), University of Washington, Fred Hutch Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, Celgene, Merck KGaA, Les Laboratories Pierre Fabre, Radius Health, Denali Therapeutics, Revolution Medicines, Relay Therapeutics, Puma Biotechnology, MacroGenics, G1 Therapeutics, Seagen, Eisai, Astellas Pharma, Servier, Menarini Group, Genentech, Daiichi Sankyo Europe
OpenAlex ID: W4392298786