García-Estévez L, Bardia A, Rugo H S, Carey L A, Diéras V C, Loibl S, Piccart M, Gianni L, Kalinsky K, O'Shaughnessy J, Hurvitz S A, Harting E, Valdez T, Phan S, Lai C, Cortés J
MD Anderson Cancer Center, Madrid, Spain.
David Geffen School of Medicine, University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, USA.
ESMO Open. 2025 Jun;10(6):105294. doi: 10.1016/j.esmoop.2025.105294. Epub 2025 Jun 2.
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.
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/m), overweight (25 to <30 kg/m), and obese (≥30 kg/m).
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.
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.
戈沙妥珠单抗（SG）是一种靶向滋养层细胞表面抗原2的抗体偶联药物（ADC），基于III期ASCENT研究结果，已在多个国家获批用于复发/难治性转移性三阴性乳腺癌（mTNBC）。近几十年来，肥胖发生率已发展到流行程度；目前尚不清楚这对治疗结果有何影响，尤其是对于像SG这种基于体重给药的ADC。我们报告了ASCENT研究中mTNBC患者的体重指数（BMI）与SG对比化疗的疗效和安全性之间的关联。
这项特设亚组分析纳入了ASCENT意向性治疗人群中接受10mg/kg体重SG或化疗的患者。在基线时评估的BMI分为正常（18.5至<25kg/m²）、超重（25至<30kg/m²）和肥胖（≥30kg/m²）。
共纳入509例患者。在所有BMI亚组的患者中，与化疗相比，SG组观察到更长的无进展生存期[正常：4.2个月对2.1个月，风险比（HR）0.48，95%置信区间（CI）0.34 - 0.67，P < 0.0001；超重：4.6个月对1.5个月，HR 0.31，95%CI 0.20 - 0.47，P < 0.0001；肥胖：5.9个月对2.6个月，HR 0.34，95%CI 0.21 - 0.53，P < 0.0001]。与化疗相比，SG在所有评估的BMI亚组中也导致总生存期和客观缓解率提高。接受SG治疗时，超重和肥胖BMI患者中≥3级治疗中出现的不良事件以及导致剂量减少和研究药物中断的不良事件发生率高于正常BMI患者；然而，各亚组的治疗中断率仍然较低且相似。
据我们所知，这是第一项评估BMI与ADC治疗结果之间关联的研究。在ASCENT研究的所有评估BMI亚组中，SG对比化疗显示出更好的疗效和可管理的安全性。
