Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Hope S Rugo; Sara M Tolaney; Delphine Loirat; Kevin Punie; Aditya Bardia; Sara A Hurvitz; Joyce O'Shaughnessy; Javier Cortés; Véronique Diéras; Lisa A Carey; Luca Gianni; Martine J Piccart; Sibylle Loibl; David M Goldenberg; Quan Hong; Martin Olivo; Loretta M Itri; Kevin Kalinsky

doi:10.1038/s41523-022-00467-1

Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

NPJ Breast Cancer. 2022 Aug 29;8(1):98. doi: 10.1038/s41523-022-00467-1.

Authors

Hope S Rugo¹, Sara M Tolaney², Delphine Loirat³, Kevin Punie⁴, Aditya Bardia⁵, Sara A Hurvitz⁶, Joyce O'Shaughnessy⁷, Javier Cortés^{8

9

10}, Véronique Diéras¹¹, Lisa A Carey¹², Luca Gianni¹³, Martine J Piccart¹⁴, Sibylle Loibl¹⁵, David M Goldenberg¹⁶, Quan Hong¹⁶, Martin Olivo¹⁶, Loretta M Itri¹⁶, Kevin Kalinsky^{17

18}

Affiliations

¹ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Hope.Rugo@ucsf.edu.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Department of Medical Oncology and D3i, Institut Curie, Paris, France.
⁴ Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
⁵ Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁶ Medical Oncology, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
⁷ Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA.
⁸ International Breast Cancer Center (IBCC), Quiron Group, Madrid & Barcelona, Barcelona, Spain.
⁹ Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.
¹⁰ Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain.
¹¹ Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
¹² Department of Hematology and Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
¹³ Gianni Bonadonna Foundation, Milano, Italy.
¹⁴ Medical Oncology, Institute Jules Bordet, Brussels, Belgium.
¹⁵ Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany.
¹⁶ Department of Clinical Development, Immunomedics, Inc., Morris Plains, NJ, USA.
¹⁷ Columbia University Irving Medical Center, New York, NY, USA.
¹⁸ Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Abstract

Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG.