Rociletinib, a third generation EGFR tyrosine kinase inhibitor: current data and future directions

ABSTRACT

Introduction: Major advances have been made since the discovery of driver mutations and their targeted therapies, especially in the treatment of patients with epidermal growth factor receptor (EGFR) mutations. Despite their initial efficacy in the majority of the patients with such driver mutations, all targeted therapies are limited by the eventual development of resistance mechanisms.

Areas Covered: EGFR T790M mutation is a common resistance mechanism after treatment with first or second generation EGFR tyrosine kinase inhibitors (TKI). Rociletinib is one of the third generation EGFR TKIs with activity against T790M and activating EGFR mutations while sparing the wild-type EGFR. In this review, we discuss the current understanding and available data on rociletinib, including the side effects associated with the medication. We will also review the BEAMing plasma test to detect T790M mutation without the need for repeat biopsy. Lastly, we review the potential resistance mechanisms after progression on rociletinib, and future directions.

Expert Opinion: It is important to note that there are other 3^rd generation EGFR TKIs with activity against T790M already approved by the US FDA (osimertinib) and many others in development. Future research will focus on figuring out which patients can benefit the most from a particular medication with minimal side effects, and further resistance mechanisms after rociletinib.

KEYWORDS:

• Rociletinib
• epidermal growth factor receptor (EGFR)
• T790M
• tyrosine kinase inhibitor

Declaration of interest

H Wakelee served as the site Principal Investigator at Stanford University for the TIGER-X clinical trial and research support for conduct of the trial was received by Stanford University. She also received research support from Clovis Oncology for trial conduct and travel support to attend an investigator meeting. 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.