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Current Oncology
Volume 29
Issue 4
10.3390/curroncol29040176
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Article

Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study

by
Fiona Turkes
1,
Annette Bryant
1,
Ruwaida Begum
1,
Michael Davidson
1,
Eleftheria Kalaitzaki
1,
Maria Aresu
1,
Retchel Lazaro-Alcausi
1,
Jane Bryant
1,
Isma Rana
1,
Sue Chua
1,
Lauren Aronson
2,
Sanna Hulkki-Wilson
1,
Charlotte Fribbens
1,
David Watkins
1,
Sheela Rao
1,
Naureen Starling
1,
David Cunningham
1,
Irene Y. Chong
2 and
Ian Chau
1,*
1
Royal Marsden NHS Foundation Trust, Downs Road, Surrey SM2 5PT, UK
2
Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2022, 29(4), 2174-2184; https://doi.org/10.3390/curroncol29040176
Submission received: 3 February 2022 / Revised: 2 March 2022 / Accepted: 14 March 2022 / Published: 22 March 2022
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Abstract

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.
Keywords: oesophagogastric cancer; HER2; c-MYC; ibrutinib oesophagogastric cancer; HER2; c-MYC; ibrutinib

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MDPI and ACS Style

Turkes, F.; Bryant, A.; Begum, R.; Davidson, M.; Kalaitzaki, E.; Aresu, M.; Lazaro-Alcausi, R.; Bryant, J.; Rana, I.; Chua, S.; et al. Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study. Curr. Oncol. 2022, 29, 2174-2184. https://doi.org/10.3390/curroncol29040176

AMA Style

Turkes F, Bryant A, Begum R, Davidson M, Kalaitzaki E, Aresu M, Lazaro-Alcausi R, Bryant J, Rana I, Chua S, et al. Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study. Current Oncology. 2022; 29(4):2174-2184. https://doi.org/10.3390/curroncol29040176

Chicago/Turabian Style

Turkes, Fiona, Annette Bryant, Ruwaida Begum, Michael Davidson, Eleftheria Kalaitzaki, Maria Aresu, Retchel Lazaro-Alcausi, Jane Bryant, Isma Rana, Sue Chua, and et al. 2022. "Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study" Current Oncology 29, no. 4: 2174-2184. https://doi.org/10.3390/curroncol29040176

APA Style

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, I. Y., & Chau, I. (2022). Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study. Current Oncology, 29(4), 2174-2184. https://doi.org/10.3390/curroncol29040176

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