1031 Background: The JCOG1607, HERB TEA Study, is a phase III trial that compared trastuzumab emtansine (T-DM1) with the HPD regimen (trastuzumab, pertuzumab, docetaxel) in older patients with advanced HER2-positive breast cancer. The primary objective was to confirm the non-inferiority of T-DM1 to HPD in overall survival (OS), with a margin of 1.35 for hazard ratio (HR). The trial was terminated early due to futility at the planned first interim analysis. T-DM1 didn't show non-inferiority to HPD in OS (HR 1.263; 95% confidence interval [CI], 0.677-2.357). Median progression-free survival (PFS) was 11.3 months for T-DM1 and 15.6 months for HPD (HR 1.373; 95% CI, 0.917-2.056). However, the condition of older patients varies widely, and we conducted a subgroup analysis to investigate the subgroup that could benefit from T-DM1 with fewer side effects as a first-line treatment. Methods: Subgroup analysis for OS and PFS involved 148 patients enrolled in JCOG1607, considering age and PS (<75 years old and PS 0,1 or <75 years old and PS 2 or ≥75 years old), Geriatric 8 (G8) score (≥15 or <15), Instrumental Activity of Daily Living (IADL) score (8 or <8), visceral/brain metastasis presence (with or without), and other factors. Results: Subgroup of <75 and PS 2 was not evaluable. For OS, HR of T-DM1 arm to HPD arm was 0.749 (95% CI: 0.310-1.808) in the group aged <75 years, while 2.867 (95%CI: 1.018-8.069) in the group aged ≥75 years (Table). G8 score and the IADL score did not show significant differences in HR for OS, although low G8 score group and low IADL score group tended to have higher OS in HPD arm than T-DM1 arm: HR of T-DM1 arm to HPD arm of 1.541 (95% CI: 0.755-3.142) in low G8 score group and 2.147 (95% CI: 0.656-7.025) in low IADL score group. For PFS, patients with visceral/brain metastasis had HR of T-DM1 arm to HPD arm of 1.794 (95% CI: 1.092-2.948). No other subgroup showed a significant difference in HR for PFS. Conclusions: No subgroups benefiting from T-DM1 as first-line treatment were identified. HPD remains the standard for advanced HER2-positive breast cancer, regardless of age (even in ≥75 years) G8 score, or IADL. Clinical trial information: UMIN000030783. [Table: see text]