Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study.
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Date
2022-03-22ICR Author
Author
Turkes, F
Bryant, A
Begum, R
Davidson, M
Kalaitzaki, E
Aresu, M
Lazaro-Alcausi, R
Bryant, J
Rana, I
Chua, S
Aronson, L
Hulkki-Wilson, S
Fribbens, C
Watkins, D
Rao, S
Starling, N
Cunningham, D
Chong, IY
Chau, I
Type
Journal Article
Metadata
Show full item recordAbstract
Oesophagogastric (OG) cancer is a highly lethal disease requiring novel treatment options. c-MYC and/or HER-2 amplified oesophageal cancer models have demonstrated sensitivity to BTK inhibition with ibrutinib. We evaluated the safety and efficacy of ibrutinib in patients with c-MYC and/or HER2 amplified pre-treated advanced OG cancer. c-MYC and HER2 amplification status were determined by FISH. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DC) at 8 weeks, safety, progression-free survival (PFS) and overall survival (OS). Eleven patients were enrolled. Eight patients had c-MYC amplified tumours, six were HER2 amplified and three were c-MYC and HER2 co-amplified. Grade ≥ 3 adverse events were fever, neutropenia, and vomiting. Grade ≥ 3 gastrointestinal haemorrhage occurred in three patients and was fatal in two cases. Among seven evaluable patients, three patients (43%) achieved a best response of SD at 8 weeks. No PR or CR was observed. Disease control was achieved for 32 weeks in one patient with a dual c-MYC and HER2 highly co-amplified tumour. The median PFS and OS were 1.5 (95% CI: 0.8-5.1) and 5.1 (95% CI: 0.8-14.5) months, respectively. Ibrutinib had limited clinical efficacy in patients with c-MYC and/or HER2 amplified OG cancer. Unexpected gastrointestinal bleeding was observed in 3 out of 8 treated patients which was considered a new safety finding for ibrutinib in this population.
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Subject
Humans
Esophageal Neoplasms
Piperidines
Adenine
Progression-Free Survival
Research team
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Language
eng
Date accepted
2022-03-14
License start date
2022-03-22
Citation
Current oncology (Toronto, Ont.), 2022, 29 (4), pp. 2174 - 2184
Publisher
MDPI