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 receptor 2–positive (HER2+) unresectable/metastatic gastric cancer (GC)/gastroesophageal junction adenocarcinoma (GEJA).
Year: 2026
Type: conference-abstract
Abstract: 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
Source: Journal of Clinical Oncology
Authors: Kohei Shitara, Aziz Zaanan, Sara Lonardi, Christelle de la Fouchardière, Clélia Coutzac, Eric Van Cutsem, Jeroen Dekervel, Lin Shen, Fabio André Franke, Yelena Y. Janjigian, Josep Tabernero, Chloe Spalding, Meredith Venerus, Fabricio Souza, Alessandro Ghiretti, Mahmut Gumus, Filippo Pietrantonio
Institutions: National Cancer Center Hospital East, Université Paris Cité, Hôpital Européen Georges-Pompidou, Istituto Oncologico Veneto, Centre Léon Bérard, Universitair Ziekenhuis Leuven, KU Leuven, Peking University Cancer Hospital, Memorial Sloan Kettering Cancer Center, Universitat de Vic - Universitat Central de Catalunya, Vall d'Hebron Institute of Oncology, Daiichi Sankyo (Germany), Daiichi Sankyo (United States), Istanbul Medeniyet University, Fondazione IRCCS Istituto Nazionale dei Tumori
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7162503486
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