Abstract P5-16-07: Assessment of sacituzumab govitecan (SG) in Black patients (pts) from the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC)
Authors: Carey Lisa A. , Zelnak Amelia , Rugo Hope S. , Dalenc Florence , Nanda Rita , Danso Michael , Saghatchian Mahasti , Kalinsky Kevin , Firmin Nelly , Ruiz-Borrego Manuel , Favret Anne , Sun Jun , Schwartzberg Lee , Hilton Christie , Omene Coral , Young Robyn , Hurvitz Sara A. , Harting Eliza , Phan See , Bardia Aditya 
Published: March 2022

Abstract
Background: Black women have higher incidence rates of TNBC and may experience worse clinical outcomes compared with White women with TNBC, due to disparities, comorbidities, or differences in TNBC biology (Dietze EG, et al. Nat Rev Cancer. 2015;15:248-254). As a result, Black pts with TNBC may benefit from novel therapies to improve outcomes. SG is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received FDA approval for pts with mTNBC who received ≥2 prior chemotherapies (at least 1 in the metastatic setting). The confirmatory phase 3 ASCENT study (NCT02574455) in pts treated in second line or greater (2L+) mTNBC setting demonstrated a significant survival benefit of SG over single-agent chemotherapy treatment of physician’s choice (TPC; median progression-free survival, [PFS]: 4.8 vs 1.7 mo, HR 0.43, P&lt;0.001; median overall survival [OS]: 11.8 vs 6.9 mo, HR 0.51) in the full trial population, with a manageable safety profile. To better understand the clinical outcomes of Black pts in the ASCENT study, a subgroup analysis was performed. Methods: In ASCENT, pts with mTNBC refractory to or relapsing after ≥2 prior chemotherapies (at least 1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative pts. Secondary endpoints included OS, objective response rate (ORR), clinical benefit rate (CBR), and safety. Race was self-reported and a prespecified subgroup for efficacy analyses. In this subgroup analysis, efficacy outcomes were assessed in the full trial population (including pts with and without known brain metastases) of pts reporting Black race; safety was analyzed in pts who received ≥1 dose of study drug in this subgroup. Results: Of the 529 pts in the full trial population, 62 (12%) pts who received SG (n=28) or TPC (n=34) were Black pts (median age, 54 y [range, 32-75] with a median of 4 prior anticancer regimens [range, 2-10]; 2 pts (3%) were positive for BRCA1/2 mutations). Characteristics were generally balanced across treatment arms. Median duration of treatment was 5.3 vs 1.6 mo in the SG vs TPC arms, respectively. In this subgroup, median PFS was improved with SG vs TPC (5.4 vs 2.2 mo; HR, 0.44; 95% CI, 0.24-0.80; P=0.008) as were ORR (32% vs 6%; odds ratio, 7.6; 95% CI, 1.5-38.8; P=0.008) and CBR (43% vs 15%; odds ratio, 4.4; 95% CI, 1.3-14.6; P=0.014). Median OS was numerically longer with SG vs TPC (13.8 vs 8.5 mo; HR, 0.64; 95% CI, 0.34-1.19; P=0.159). The safety profile of SG in Black pts was similar to that of the full trial population. Key treatment-related adverse events (TRAEs) of grade ≥3 in this subgroup (SG vs TPC) were neutropenia (48% vs 42%), anemia (12% vs 6%), leukopenia (8% vs 16%), and febrile neutropenia (8% vs 3%). No pts in the SG arm discontinued due to TRAEs; 1 pt in the TPC (3%) arm discontinued due to TRAEs. There were no treatment-related deaths. Conclusions: While only 12% of pts in the ASCENT trial self-identified as Black, Black pts with pretreated mTNBC derived a similar clinical benefit from SG over TPC as seen in the full trial population, with a manageable safety profile. SG should be considered as a treatment option for pts with mTNBC in the 2L+ setting.
Citation Format: Lisa A. Carey, Amelia Zelnak, Hope S. Rugo, Florence Dalenc, Rita Nanda, Michael Danso, Mahasti Saghatchian, Kevin Kalinsky, Nelly Firmin, Manuel Ruiz-Borrego, Anne Favret, Jun Sun, Lee Schwartzberg, Christie Hilton, Coral Omene, Robyn Young, Sara A. Hurvitz, Eliza Harting, See Phan, Aditya Bardia. Assessment of sacituzumab govitecan (SG) in Black patients (pts) from the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-07.