An extended phase Ib study of epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours

Arkenau, H.-T. et al. (2018) An extended phase Ib study of epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours. European Journal of Cancer, 103, pp. 17-23. (doi: 10.1016/j.ejca.2018.07.134) (PMID:30196106)

Abstract

Background: Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity. Patients and Methods: Patients with solid tumours expressing EGFR or HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7 days, followed by continuous once-daily dosing from Day 8. Results: We treated 76 patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade I and II adverse events (AEs). The most frequent AE was diarrhoea, which was generally manageable with loperamide. The objective response rate (ORR) in patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs) and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive tumours; the ORR for HER2-positive breast and upper GI cancer populations was 19.0% and 20.0%. Partial response in the brain disease of one breast cancer patient lasted 7.5 months. Conclusion: Once-daily dosing of epertinib at 800 mg was well-tolerated and demonstrated promising antitumour activity in patients with heavily pretreated HER2-positive breast and upper GI cancer, including those with brain metastases. EudraCT number: 2009-017817-31.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wilson, Professor Richard
• Authors: Arkenau, H.-T., Italiano, A., Mak, G., Toulmonde, M., Baird, R.D., Garcia-Corbacho, J., Plummer, R., Flynn, M., Forster, M., Wilson, R.H., Tosi, D., Adenis, A., Donaldson, K., Posner, J., Kawabata, I., Arimura, A., Deva, S., and Spicer, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: European Journal of Cancer
• Publisher: Elsevier
• ISSN: 0959-8049
• ISSN (Online): 1879-0852
• Published Online: 06 September 2018
• Copyright Holders: Copyright © 2018 Elsevier
• First Published: First published in European Journal of Cancer 103:17-23
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher