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.
Study Details
The multicenter trial included two cohorts of patients with locally advanced or metastatic HER2-low disease enrolled between February 2018 and February 2019:
- Cohort 1 included 21 patients with immunohistochemistry 2+/in situ hybridization–negative HER2 status
- Cohort 2 included 24 patients with immunohistochemistry 1+ status.
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.
Key Findings
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.
