A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) …

HJ Mackay, HJ Au, E McWhirter, T Alcindor… - Investigational new …, 2012 - Springer
HJ Mackay, HJ Au, E McWhirter, T Alcindor, A Jarvi, K MacAlpine, L Wang, JJ Wright…
Investigational new drugs, 2012Springer
Summary Purpose The Src family of kinases may play a role in the development and
progression of gastric cancer. We evaluated the activity and safety of saracatinib an oral,
anilinoquinazolone, non-receptor tyrosine kinase inhibitor targeting Src kinases, in patients
with metastatic or locally advanced gastric carcinoma. Methods Eligible patients who had
received≤ 1 prior line of chemotherapy for metastatic disease received saracatinib 175
mg/day of a 28 day cycle until progression. The primary endpoint was the objective …
Summary
Purpose The Src family of kinases may play a role in the development and progression of gastric cancer. We evaluated the activity and safety of saracatinib an oral, anilinoquinazolone, non-receptor tyrosine kinase inhibitor targeting Src kinases, in patients with metastatic or locally advanced gastric carcinoma. Methods Eligible patients who had received ≤1 prior line of chemotherapy for metastatic disease received saracatinib 175 mg/day of a 28 day cycle until progression. The primary endpoint was the objective response and/or prolonged stable disease rate (pSD ≥ 16 weeks). Results Ten patients with gastric carcinoma and 11 with adenocarcinoma of the gastroesophageal junction received a median of 2 cycles (range 1–10 cycles) of treatment per patient. 17 patients were evaluable for response. No objective response was seen. One patient experienced prolonged Stable disease (pSD). Three patients had SD and 13 progressive disease. Median overall survival was 7.8 months (95% CI, 3.9–12.2 months) and median time to progression was 1.8 months (95% CI: 1.5–1.9 months). Grade 3 events possibly related to saracatinib included: fatigue (2 patients), hypoxia (2) anemia (3) and lymphopenia (2). Conclusion Saracatinib has insufficient activity as a single agent in patients with advanced gastric adenocarcinoma to warrant further investigation. Further development in gastric cancer would require rational drug combinations or identification of a tumor phenotype sensitive to Src inhibition.
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