Dacomitinib: an investigational drug for the treatment of glioblastoma

ABSTRACT

Introduction: Standard treatment of newly diagnosed glioblastoma (GB) is surgery with radiotherapy and temozolomide, but tumors will recur with a median overall survival of only 15 months. It seems imperative to explore new possibilities of treatment based on targetable alterations known to be present in GB. Among others, Epidermal Growth Factor Receptor or EGFR (HER1) mutations or amplifications are the most prevalent alterations in GB. In fact, around 40% of GB cases show amplification of EGFR gene, and half of these patients carry the EGFRvIII mutation, a deletion that generates a continuous activation of the tyrosine kinase domain of the receptor.

Areas covered: We review the current knowledge about Dacomitinib, an oral, irreversible, second-generation, pan-HER tyrosine kinase inhibitor, in the treatment of glioblastoma. Dacomitinib has noteworthy antiglioma activity in preclinical models and has been tested in one phase II trial in patients with recurrent GB with EGFR amplification.

Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit. Therefore, it is necessary to improve the knowledge about the mechanisms of failure or resistance to EGFR inhibitors in GB.

KEYWORDS:

• Dacomitinib
• EGFR
• EGFR tyrosine kinase inhibitor
• glioblastoma
• high grade glioma
• tyrosine kinase inhibitors

Box 1. Drug summary.

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Declaration of Interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

R.G. has been funded by the AECC Scientific Foundation. Research has been funded by grants from the Ministerio de Economía y Competitividad: PSG, (MINECO-RETOS) SAF2015-65175-R to PSG and (MINECO-EXCELENCIA) BFU2015-65685P to SCT.