Clinical Impact of Trastuzumab Deruxtecan in Patients With HER2-Positive Advanced Gastric Cancer and Ascites: Findings From the EN-DEAVOR Study.

PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) and ascites have poor prognosis and are often excluded from clinical trials. Thus, evidence on the effect of trastuzumab deruxtecan (T-DXd) in this population remains limited.

MATERIALS AND

METHODS

This subgroup analysis of the EN-DEAVOR (UMIN000049032) study assessed outcomes in patients with T-DXd-treated HER2-positive AGC from Japan, stratified by computed tomography-defined ascites severity: none (ascites not detected), low (confined to the upper or lower abdomen), moderate (neither low nor high), and high (diffusely present throughout the abdomen). The outcomes included overall survival (OS), real-world progression-free survival (rwPFS), ascites response rate, and incidence of grade ≥3 adverse events (AEs).

RESULTS

Among 312 patients, 173, 81, 34, and 20 had no, low, moderate, and high ascites severity, respectively. The median OS was 12.35, 6.77, 6.97, and 5.13 months, respectively, and the median rwPFS was 5.32, 3.68, 3.50, and 2.76 months, respectively, for the no, low, moderate, and high severity groups. The overall ascites response rate to ascites severity was 23.0%. The median OS and rwPFS were 11.83 (95% confidence interval [CI], 7.82-18.96) and 6.64 (95% CI, 4.17-9.56) months, respectively, in responders, and 6.28 (95% CI, 4.90-7.03) and 3.15 (95% CI, 2.17-3.94) months, respectively, in non-responders. Grade ≥3 AE incidence was comparable across subgroups.

CONCLUSIONS

T-DXd demonstrated efficacy and a manageable safety profile in patients with HER2-positive AGC, including those with severe ascites. The ascites response correlated with improved outcomes.