Abstract PS11-09: Impact of UGT1A1 status on the safety profile of sacituzumab govitecan in the phase 3 ASCENT study in patients with metastatic triple-negative breast cancer
Authors: Rugo Hope S. , Tolaney Sara M. , Loirat Delphine , Punie Kevin , Bardia Aditya , Hurvitz Sara A. , O'Shaughnessy Joyce , Cortés Javier , Diéras Véronique , Carey Lisa , Gianni Luca , Piccart Martine J. , Loibl Sibylle , Goldenberg David M. , Hong Quan , Olivo Martin , Itri Loretta M. , Kalinsky Kevin 
Published: February 2021

Abstract
Background: Trophoblast cell-surface antigen-2 (Trop-2) is highly expressed in many epithelial tumors, including triple-negative breast cancer (TNBC). Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan, via a unique hydrolyzable linker that allows SN-38 release intracellularly and in the tumor microenvironment (bystander effect). SG received accelerated approval in April 2020 for the treatment of patients with metastatic TNBC (mTNBC) who received at least 2 prior therapies for metastatic disease. The most common adverse events (AEs) observed with SG are neutropenia and gastrointestinal toxicity, also seen with irinotecan. To provide further information on SG, additional safety analyses from ASCENT, a randomized, phase 3 confirmatory study of SG versus standard-of-care chemotherapy in patients with mTNBC, will be reported. Methods: In the global, multicenter, open-label, phase 3 ASCENT study (NCT02574455), 529 patients with mTNBC refractory to or relapsing after at least 2 prior chemotherapies were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8 every 21 days) or single-agent treatment of physician’s choice (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival measured by central independent review per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, overall survival, and safety. An exploratory analysis of incidence of grade 3-5 AEs by UGT1A1 genotype was also performed. Post-hoc analysis of the time to onset and duration of key AEs will be performed, and descriptive analyses on alopecia, nausea and vomiting will also be provided. Results: Exploratory safety analyses by UGT1A1 allele status will be shown as well as time to onset and duration of neutropenia and diarrhea. Further descriptive analyses on alopecia, nausea, and vomiting will be provided along with AE management strategies. Conclusions: These analyses will provide further insights into the safety profile of SG and appropriate AE management strategies for patients with previously treated mTNBC to allow optimal therapeutic exposure.
Citation Format: Hope S. Rugo, Sara M. Tolaney, Delphine Loirat, Kevin Punie, Aditya Bardia, Sara A. Hurvitz, Joyce O'Shaughnessy, Javier Cortés, Véronique Diéras, Lisa Carey, Luca Gianni, Martine J. Piccart, Sibylle Loibl, David M. Goldenberg, Quan Hong, Martin Olivo, Loretta M. Itri, Kevin Kalinsky. Impact of UGT1A1 status on the safety profile of sacituzumab govitecan in the phase 3 ASCENT study in patients with metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-09.