Additional health-related quality of life (HRQoL) analysis from DESTINY-Gastric04 (DG-04), a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in patients (pts) with human epidermal growth factor recep

4111 Background: In DG-04 (NCT04704934), a statistically significant and clinically meaningful improvement in overall survival was seen with T-DXd vs RAM + PTX in pts with HER2+ unresectable/metastatic GC/GEJA in the second-line setting. Patient-reported HRQoL was also maintained with T-DXd. We report additional HRQoL results from DG-04. Methods: Pts with unresectable/metastatic GC/GEJA who were HER2+ (IHC 3+, IHC 2+/ISH+) by local or central testing received T-DXd 6.4 mg/kg or RAM + PTX. Patient-reported outcomes were assessed at prespecified time points using the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) scale and the EuroQol 5-dimension, 5-level (EQ-5D-5L) visual analog scale (VAS). Time to first deterioration (TTFD) and mean change from baseline (CFB) were assessed. Mixed model for repeated measures (MMRM) was used to analyze CFB of the FACT-Ga scale. Results: At data cutoff (October 24, 2024), median TTFD favored T-DXd (n = 246) vs RAM + PTX (n = 248) for the EQ-5D-5L VAS (3.5 vs 3.0 mo; hazard ratio [HR], 0.79; nominal P = 0.063), FACT-General (G) total score (3.5 vs 2.8 mo; HR, 0.74; nominal P = 0.015), and FACT-Ga emotional well-being (EWB; 5.1 vs 3.7 mo; HR, 0.74; nominal P = 0.026) and social well-being (SWB; 3.8 vs 2.5 mo; HR, 0.71; nominal P = 0.006) subscales. Additional TTFD results, including TTFD in gastric cancer subscale (GaCS) and physical well-being (PWB), are in the Table. Mean CFB scores remained stable in all FACT-Ga subscales, with no clinically meaningful changes associated with T-DXd. MMRM analysis of CFB results favored T-DXd vs RAM + PTX for the FACT-G total score (nominal P = 0.023), and the FACT-Ga functional well-being (FWB; nominal P = 0.045) and SWB (nominal P = 0.004) subscales. Conclusions: These findings support patient-reported HRQoL was maintained with T-DXd in pts with HER2+ unresectable/metastatic GC/GEJA. TTFD was not negatively impacted with T-DXd; mean CFB in all FACT-Ga subscales showed pt symptoms and functioning remained stable, with some subscales favoring T-DXd vs RAM + PTX. Clinical trial information: NCT04704934 . T-DXdn=246 RAM + PTXn=248 HR (95% CI)Nominal P Value EQ-5D-5L VAS, median TTFD (95% CI), mo 3.5 (2.7-5.0) 3.0 (2.1-3.5) 0.79 (0.62-1.01)0.063 FACT-Ga scale, median TTFD (95% CI), mo FACT-G (EWB + FWB + PWB + SWB) 3.5 (2.2-4.4) 2.8 (2.1-3.5) 0.74 (0.58-0.95)0.015 FACT-Ga total score (FACT-G + GaCS) 4.4 (3.5-5.7) 4.4 (3.5-6.5) 0.95 (0.73-1.24)0.700 EWB 5.1 (4.2-8.7) 3.7 (2.4-5.0) 0.74 (0.57-0.97)0.026 FWB 2.3 (2.1-3.2) 2.3 (2.1-3.5) 0.89 (0.70-1.13)0.338 PWB 2.8 (2.1-3.7) 2.2 (2.1-3.1) 0.79 (0.62-1.00)0.052 SWB 3.8 (2.6-5.3) 2.5 (2.1-3.5) 0.71 (0.55-0.91)0.006 GaCS 4.9 (3.7-6.3) 5.8 (4.8-7.4) 1.11 (0.84-1.47)0.462