Work

189P The impact of high body mass index (BMI) on the safety and efficacy of sacituzumab govitecan (SG) in patients (pts) with metastatic triple-negative breast cancer (mTNBC) from ASCENT

Year: 2024

Type: article

Abstract: SG is a Trop-2–directed antibody-drug conjugate (ADC) approved in multiple countries for the treatment of relapsed or refractory mTNBC. In the phase III ASCENT study (n = 529), significantly longer PFS (hazard ratio [HR], 0.43; 95% CI, 0.35-0.54), and OS (HR, 0.51; 95% CI, 0.41-0.62) were observed with SG vs chemotherapy treatment of physician’s choice (TPC), as of the data cutoff date of Mar 11, 2020 (median follow-up of 17.7 months). The incidence of obesity has grown to epidemic proportions in recent decades, and it is unclear what impact this may have on treatment outcomes especially for ADCs like SG which have weight-based dosing. Here, we look at the safety and efficacy of SG vs TPC among BMI subgroups. This ad hoc subgroup analysis included pts from the full intent-to-treat population of ASCENT who received SG at 10 mg/kg of body weight or TPC. BMI was assessed at baseline and was classified as follows: underweight/normal (< 25 kg/m2), overweight (25 - < 30 kg/m2), and obese (≥ 30 kg/m2). As of Feb 25, 2021, longer PFS and OS, and higher ORR were observed with SG compared with TPC in pts from all BMI subgroups (Table). Grade ≥ 3 treatment-emergent adverse events (TEAEs) were observed in 68%, 78%, and 77% of pts treated with SG in the underweight/normal, overweight, and obese subgroups, respectively. TEAEs leading to dose reductions were observed in 11%, 24%, and 41% of pts, respectively, and TEAEs leading to treatment discontinuation were observed in 4%, 3%, and 8%, respectively.Table: 189PUnderweight/Normal(< 25 kg/m2)46%Overweight(25 - < 30 kg/m2)29%Obese(≥ 30 kg/m2)25%SG n = 127TPC n = 114SG n = 71TPC n = 84SG n = 68TPC n = 64Median PFS,a mo4.21.94.61.55.92.6(95% CI)(2.9-5.6)(1.5-2.8)(3.3-6.3)(1.4-1.6)(4.1-8.3)(1.6-3.0)HR0.50.310.34(95% CI)(0.37-0.69)(0.20-0.47)(0.21-0.53)Median OS, mo10.96.210.86.714.98.7(95% CI)(9.4-13.0)(4.8-7.1)(9.0-14.2)(5.2-8.9)(11.2-16.8)(6.7-9.8)HR0.550.510.45(95% CI)(0.42-0.74)(0.35-0.74)(0.30-0.67)ORR,a %25.27.933.81.239.71.6(95% CI)(17.9-33.7)(3.7-14.5)(23.0-46.0)(0.0-6.5)(28.0-52.3)(0.0-8.4)aIndependent review.ORR, objective response rate; OS, overall survival; PFS, progression-free survival. Open table in a new tab aIndependent review. ORR, objective response rate; OS, overall survival; PFS, progression-free survival. To our knowledge, this is the first study evaluating the impact of BMI on treatment with ADCs. SG demonstrated improved efficacy vs TPC and a manageable safety profile in all evaluated BMI subgroups from ASCENT. Although a larger proportion of pts with high BMI (especially obese pts) had SG dose reduction, this did not translate into a decrease in efficacy.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2024.103211