The association of high body mass index with the safety and efficacy of sacituzumab govitecan in patients with metastatic triple-negative breast cancer from the ASCENT study

ESMO Open. 2025 Jun;10(6):105294. doi: 10.1016/j.esmoop.2025.105294. Epub 2025 Jun 2.

Abstract

Background: Sacituzumab govitecan (SG) is a trophoblast cell-surface antigen 2-directed antibody-drug conjugate (ADC) approved in multiple countries for relapsed/refractory metastatic triple-negative breast cancer (mTNBC) based on results from the phase III ASCENT study. The incidence of obesity has grown to epidemic proportions in recent decades; it is unclear what impact this has on treatment outcomes, especially for ADCs like SG that have weight-based dosing. We report the association of body mass index (BMI) with efficacy and safety of SG versus chemotherapy among patients with mTNBC from the ASCENT study.

Patients and methods: This ad hoc subgroup analysis included patients from the intent-to-treat population of ASCENT who received SG at 10 mg/kg of body weight or chemotherapy. BMI, assessed at baseline, was classified as normal (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and obese (≥30 kg/m2).

Results: A total of 509 patients were included. Longer progression-free survival was observed with SG versus chemotherapy in patients from all BMI subgroups [normal: 4.2 versus 2.1 months, hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.34-0.67, P < 0.0001; overweight: 4.6 versus 1.5 months, HR 0.31, 95% CI 0.20-0.47, P < 0.0001; obese: 5.9 versus 2.6 months, HR 0.34, 95% CI 0.21-0.53, P < 0.0001]. SG also led to improved overall survival and objective response rates versus chemotherapy in all evaluated BMI subgroups. With SG treatment, the incidence of treatment-emergent adverse events of grade ≥3, and those leading to dose reductions and study drug interruptions, was higher in patients with overweight and obese BMI compared with normal BMI; however, the rates of treatment discontinuation remained low and similar across the subgroups.

Conclusions: To our knowledge, this is the first study evaluating the association of BMI with outcomes with ADCs. SG demonstrated improved efficacy versus chemotherapy and a manageable safety profile in all evaluated BMI subgroups from ASCENT.

Keywords: antibody–drug conjugate; body mass index; metastatic triple-negative breast cancer; obesity; sacituzumab govitecan.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Body Mass Index*
  • Camptothecin* / administration & dosage
  • Camptothecin* / adverse effects
  • Camptothecin* / analogs & derivatives
  • Camptothecin* / therapeutic use
  • Female
  • Humans
  • Immunoconjugates* / adverse effects
  • Immunoconjugates* / therapeutic use
  • Middle Aged
  • Neoplasm Metastasis
  • Obesity / complications
  • Treatment Outcome
  • Triple Negative Breast Neoplasms* / complications
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / mortality
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • sacituzumab govitecan
  • Camptothecin
  • Immunoconjugates