Safety Analyses from the Phase 3 ASCENT Trial of Sacituzumab Govitecan in Metastatic Triple-negative Breast Cancer

Overview

Journal NPJ Breast Cancer

Date 2022 Aug 29

PMID 36038616

Authors

Hope S Rugo

Sara M Tolaney

Delphine Loirat

Kevin Punie

Aditya Bardia

Sara A Hurvitz

Joyce OShaughnessy

Javier Cortes

Veronique Dieras

Lisa A Carey

Luca Gianni

Martine J Piccart

Sibylle Loibl

David M Goldenberg

Quan Hong

Martin Olivo

Loretta M Itri

Kevin Kalinsky

Affiliations

Soon will be listed here.

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.

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