Trastuzumab deruxtecan in advanced gastric tumors

The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has shown preliminary clinical activity in patients with heavily pretreated HER2–low gastric/gastroesophageal junction adenocarcinoma, with a profile safety consistent with the manageable safety profile of T-DXd. Data were recently published on Journal of Clinical Oncology.

The study enrolled patients with locally advanced or metastatic HER2-low, gastric/ gastroesophageal junction adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive; participants received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The confirmed objective response rate ranged from 9.5% in an immunoistochemistry positive cohort (cohort 2) to 26.3% in a immunohistochemistry positive/in situ hybridization–negative cohort (cohort 1); the median overall survival ranged from 7.8 months in cohort 1 to 8.5 in cohort 2 and the median progression-free survival was 4.4 months and 2.8 months respectively; 68.4% of patients in cohort 1 and 60.0% in cohort 2 experienced reduced tumor size and safety profile was consistent with T-DXd manageable safety profile. «This study supports preclinical studies and early-phase clinical investigation that indicated an antitumor effect of T-DXd in HER2-low tumors, including gastric cancers», authors say. The trial has some relevant limitations, including the small patient numbers, a low disease burden (47.7% of patients had baseline sum of measurable tumors < 5 cm) and patients ethnicity: they were all from Japan and South Korea, so the results should be confirmed in other populations. However, as authors conclude, «This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/gastroesophageal junction adenocarcinoma. Additional randomized controlled trials in larger cohorts are required to determine the efficacy and safety of T-DXd in this settings».