Rapid Readouts: Phase 3 ASCENT Study for Metastatic Triple-Negative Breast Cancer

Hope S. Rugo, MD, FASCO, discusses data from the following presentation:

• Assessment of Sacituzumab Govitecan vs Treatment of Physician’s Choice Cohort by Agent in the Phase 3 ASCENT Study of Patients with Metastatic Triple-Negative Breast Cancer. (O’Shaughnessy, ASCO 2021, Abstract 1077)
  • The objective of this study is to report results in patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan or treatment of physician’s choice (TPC).
  • Sacituzumab govitecan (SG) is an antibody-drug conjugate comprised of an anti–Trop-2 antibody coupled to a cytotoxic SN-38 through a hydrolyzable linker.
  • 529 patients with mTNBC who had received ≥ 2 prior chemotherapies were randomly assigned 1:1 to either SG 10 mg/kg intravenously on days 1 & 8, every 21-day cycle (n=267), or treatment of physician’s choice (capecitabine, eribulin, vinorelbine, or gemcitabine) (n=262).
  • Efficacy outcomes were assessed in the brain metastases-negative population for each agent:
    • Progression-free survival (PFS) assessed by blinded independent central review per RECIST 1.1.
    • Secondary end points were objective response rate (ORR) assessed by blinded independent central review per RECIST 1.1, duration of response, overall survival (OS), and safety.
  • Conclusions: efficacy
    • SG resulted in longer median PFS vs each TPC agent (eribulin, vinorelbine, capecitabine, gemcitabine): 5.6 vs 2.1, 1.6, 1.6, and 2.7 months, respectively.
    • SG treatment also resulted in longer median OS vs eribulin, vinorelbine, capecitabine, or gemcitabine (12.1 vs 6.9, 5.9, 5.2, and 8.4 months, respectively).
    • The ORR (35% vs 5%, 4%, 6%, and 3%) and clinical benefit rate (45% vs 8%, 6%, 10%, and 14%) were higher with SG vs eribulin, vinorelbine, capecitabine, or gemcitabine.
    • Median duration of response for SG was 6.3 months compared to eribulin, vinorelbine, capecitabine, or gemcitabine (3.6, 2.8, not evaluable, and 2.9 months, respectively).
  • Conclusions: safety
    • Grade ≥3 treatment-related adverse events (AEs) with SG vs eribulin vs the other 3 TPC agents combined included neutropenia (51% vs 31% vs 36%), leukopenia (10% vs 5% vs 6%), diarrhea (10% vs 0% vs 1%), anemia (8% vs 2% vs 8%), febrile neutropenia (6% vs 2% vs 2%), and fatigue (2% vs 5% vs 6%).
    • SG has a manageable safety profile and low rates of discontinuation due to AEs, and no treatment-related deaths were reported.
• An efficacy benefit was seen with SG vs TPC and retained when evaluating each TPC chemotherapy agent individually.
• These results support consideration of SG as a new standard of care in patients with pretreated mTNBC.