252P Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience

Abstract

Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established. We conducted a retrospective cohort study using the nationwide US Electronic Health Record-derived de-identified Flatiron Health database. The study population included pts diagnosed with MBC from Jan 1, 2011 through Feb 30, 2021. Kendall tau correlation between each surrogate endpoint (rwPFS and TTNT) and OS was evaluated using the Hougaard copula model. Kendall’s tau (τ) was calculated in the full cohort, and within each subgroup of metastatic disease, based on their prognostic significance, as defined by the occurrence of bone metastases (mets) only (subgroup 1), non-hepatic visceral mets +/- bone mets (subgroup 2), liver mets +/- other visceral and/or bone mets (subgroup 3), and one or more brain mets +/- other types of metastasis (subgroup 4). This work was supported by the imCORE network. Overall, 9,733 patients with MBC were included. Median age was 63 years (IQR: 54-72). Regarding sites of metastatic disease, subgroup 2 was most highly represented (n=4,188; 43.0%), followed by subgroup 1 (n=2,601; 26.7%), subgroup 3 (n=2,306; 23.7%) and subgroup 4 (n=638; 6.6%). Median OS in the overall population was 32.4 mos (95%CI: 31.2-33.3). Median rwPFS was 11.5 mos (95%CI: 11.1-11.9), and median TTNT was 11.1 mos (95%CI: 10.7-11.5). In the full cohort, the correlation of rwPFS with OS was 0.54, while that of TTNT with OS was 0.47 (Table).Table: 252PMedian OS, rwPFS and TTNT and Kendall tau correlation of each pair of evaluated endpoints.Overall Population (n=9,733)Subgroup 1 (n=2,601)Subgroup 2 (n=4,188)Subgroup 3 (n=2,306)Subgroup 4 (n=638)Median OS, months (95%CI)32.4 (31.2-33.3)44.3 (42.2-46.9)32.7 (31.0-34.0)22.6 (21.3-24.4)16.6 (14.8-19.7)Median rwPFS, months (95%CI)11.5 (11.1-11.9)18.5 (16.9-19.4)11.9 (11.4-12.7)8.2 (7.7-8.9)5.9 (4.9-6.7)Median TTNT, months (95%CI)11.1 (10.7-11.5)16.2 (15.1-17.9)11.3 (10.6-12.0)8.7 (8.2-9.2)6.7 (5.7-7.6)rwPFS-OS Correlation: τ (95%CI)0.54 (0.53-0.56)0.47 (0.45-0.50)0.54 (0.52-0.56)0.57 (0.55-0.59)0.60 (0.56-0.64)TTNT-OS Correlation: τ (95%CI)0.47 (0.46-0.48)0.37 (0.34-0.40)0.45 (0.43-0.46)0.54 (0.52-0.56)0.58 (0.55-0.62) Open table in a new tab Real-world PFS (rwPFS) and TTNT may represent meaningful intermediate endpoints for OS in patients with MBC overall, and within different disease subgroups.