As reported in the Journal of Clinical Oncology by Yamaguchi et al, an exploratory cohort analysis in a Japanese/South Korean phase II trial (DESTINY-Gastric01) indicated that fam-trastuzumab deruxtecan-nxki (TDX-d) showed activity in previously treated—but anti-HER2 treatment–naive—patients with HER2-low gastric or gastroesophageal junction adenocarcinoma.
The multicenter trial included two cohorts of patients with locally advanced or metastatic HER2-low disease enrolled between February 2018 and February 2019:
Patients had disease progression after two or more prior therapies, including fluoropyrimidine and platinum, but had received no prior anti-HER2 therapy. T-DXd was given at 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed objective response rate on independent central review among patients with measurable disease at baseline.
Among 19 response-evaluable patients in cohort 1, objective responses (all partial) were observed in 5 (26.3%, 95% confidence interval [CI] = 9.1%–51.2%); tumor shrinkage was observed in 13 (68.4%), and the disease control rate was 89.5%. The median duration of response was 7.6 months (95% CI = 4.1 months to not evaluable).
This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/gastroesophageal junction adenocarcinoma.— Yamaguchi et al
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Among 21 response-evaluable patients in cohort 2, objective responses (both partial) were observed in 2 (9.5%, 95% CI = 1.2%–30.4%), tumor shrinkage was observed in 12 (57.1%), and the disease control rate was 71.4%. Response durations were 8.1 and 12.5 months, respectively.
Among all patients in cohort 1 and cohort 2, median progression-free was 4.4 months (95% CI = 2.7–7.1 months) and 2.8 months (95% CI = 1.5–4.3 months) and median overall survival was 7.8 months (95% CI = 4.7 months to not evaluable) and 8.5 months (95% CI = 4.3–10.9 months).
The most common grade ≥ 3 adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Treatment-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 and 2). No treatment-related deaths were observed.
The investigators concluded, “This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/gastroesophageal junction adenocarcinoma.”
Kensei Yamaguchi, MD, of the Cancer Institute Hospital of JFCR, Tokyo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Daiichi Sankyo Co, Ltd, and AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.