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

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.

• Authors: 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
• Journal: NPJ breast cancer (NPJ Breast Cancer) Vol. 8 Issue 1 Pg. 98 (Aug 29 2022) ISSN: 2374-4677 [Print] United States
• PMID: 36038616 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).