Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

Authors

Joyce O'Shaughnessy

Joyce O'Shaughnessy

Texas Oncology-Baylor Sammons Cancer Center, US Oncology, Dallas, TX

Joyce O'Shaughnessy , Kevin Punie , Mafalda Oliveira , Filipa Lynce , Sara M. Tolaney , Florence Dalenc , Priyanka Sharma , Michaela L. Tsai , Aditya Bardia , Javier Cortes , Michael A. Danso , Stephanie Henry , Alejandra T. Perez , Sara A. Hurvitz , Kevin Kalinsky , Quan Hong , Martin Sebastian Olivo , Loretta Itri , Hope S. Rugo

Organizations

Texas Oncology-Baylor Sammons Cancer Center, US Oncology, Dallas, TX, Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, Georgetown Lombardi Comprehensive Cancer Center and Medical Oncology, Dana-Farber Cancer Institute, Washington, DC, Dana-Farber Cancer Institute, Boston, MA, Institut Claudius Regaud–IUCT Oncopole, Toulouse, France, University of Kansas Medical Center, Westwood, KS, VPCI Oncology Research, Minneapolis, MN, Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, International Breast Cancer Center, Quiron Group, Madrid & Barcelona, Barcelona, Spain, Virginia Oncology Associates, Norfolk, VA, Department of Oncology-Hematology, Radiotherapy, and Nuclear Medicine, CHU UCL Namur, Namur, Belgium, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, Winship Cancer Institute, Emory University, Atlanta, GA, Department of Clinical Development, Immunomedics, Inc, a subsidiary of Gilead Sciences, Inc., Morris Plains, NJ, Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA

Research Funding

Pharmaceutical/Biotech Company
Immunomedics, Inc. a subsidiary of Gilead Sciences, Inc

Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). 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 accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455.

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Triple-Negative

Clinical Trial Registration Number

NCT02574455

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 1077)

DOI

10.1200/JCO.2021.39.15_suppl.1077

Abstract #

1077

Poster Bd #

Online Only

Abstract Disclosures