Abstract PO5-21-09: Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer

Abstract Background Sacituzumab govitecan (SG) is a Trop-2directed antibody-drug conjugate approved for second-line or later (2L+) treatment of metastatic triple-negative breast cancer in multiple countries and for 2L+ treatment of HR+/HER2‒ (IHC 0, 1+, or 2+/ISH) metastatic breast cancer (mBC) in the US. SG significantly improved progression-free survival (PFS) and overall survival (OS) vs treatment of physician’s choice (TPC) in patients (pts) with pretreated, endocrine-resistant HR+/HER2‒ mBC in the TROPiCS-02 study. The incidence of HR+/HER2‒ mBC increases with age, especially after 65, and older pts often have poorer prognosis due to comorbidities, increased toxicity, and reduced efficacy of chemotherapy. In TROPiCS-02, pts aged ≥ 65 years (yr) derived consistent PFS benefit and clinically meaningful improved OS with SG vs TPC. In this analysis, we present additional efficacy and safety outcomes by age subgroup. Methods Pts with HR+/HER2‒ mBC who had received at least 1 endocrine therapy, taxane, and CDK4/6 inhibitor, and 2 to 4 prior lines of chemotherapy for mBC, were randomized to either SG (10 mg/kg IV days 1 and 8, Q3W) or TPC. The primary end point was PFS, and secondary end points included OS, objective response rate (ORR), and safety. A post hoc analysis was conducted by age subgroups (< 65 vs ≥ 65, < 75 vs ≥ 75). Results In total, 543 pts were randomized to the SG (n = 272; 73 [27%] ≥ 65, 16 [6%] ≥ 75) and TPC (n = 271; 67 [25%] ≥ 65, 8 [3%] ≥ 75) groups. Baseline characteristics were generally similar across treatment arms in each age subgroup, but a higher proportion of pts had performance status 1 vs 0 in the ≥ 65 vs < 65 and ≥ 75 vs < 75 subgroups, respectively. The data cutoff date was July 1, 2022. SG demonstrated longer median PFS and OS vs TPC across age subgroups. Hazard ratios (HR) for PFS with SG vs TPC were 0.69, 0.59, 0.70, and 0.30 for the < 65, ≥ 65, < 75, and ≥ 75 subgroups, respectively (Table). The HR for OS were 0.81, 0.80, 0.82, and 0.56 in these subgroups, respectively (Table). Median duration of response (DoR) was also longer with SG vs TPC across age subgroups, although median DoR was not estimable in the ≥ 75 subgroup (Table). ORR was higher with SG vs TPC, except in the ≥ 75 subgroup (Table). Safety was generally similar with SG vs TPC across subgroups with the following differences. Grade ≥ 3 treatment-emergent adverse events were more common in the ≥ 75 subgroup than the other subgroups (SG, 81% in ≥ 75 vs 68%-73% for all others; TPC, 71% in ≥ 75 vs 60%-61% for all others). TEAEs leading to dose reduction were also more common in pts treated with SG in the ≥ 75 subgroup, but were consistent across other subgroups (Table). However, sample sizes in the ≥ 75 subgroup were small, which limits interpretation (Table). TEAEs leading to treatment discontinuation were more common in older pts, irrespective of treatment group (Table). Conclusions SG showed benefit in PFS and OS vs TPC in pts with HR+/HER2‒ mBC across age subgroups, consistent with the intent to treat population. SG was associated with a slight increase in toxicity for elderly pts, as expected. SG demonstrated a favorable benefit/risk profile, with efficacy benefit and acceptable toxicity, for elderly pts. Table. Citation Format: Aditya Bardia, Peter Schmid, Sara Tolaney, Frederik Marmé, Javier Cortés, Theresa Valdez, Hao Wang, Wendy Verret, Hope Rugo. Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-21-09.