title: Rociletinib, a third generation EGFR tyrosine kinase inhibitor: current data and future directions.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Division of Hematology and Oncology , Stanford Hospital & Clinics , Stanford , CA , USA.
authors.forename: Jody C
authors.initials: JC
authors.lastname: Chuang
authors.affiliation: a Division of Hematology and Oncology , Stanford Hospital & Clinics , Stanford , CA , USA.
authors.forename: Ameen A
authors.initials: AA
authors.lastname: Salahudeen
authors.affiliation: b Department of Medicine, Division of Oncology , Stanford University School of Medicine , Stanford , CA , USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
mesh_terms: D000178:Acrylamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C000589977:rociletinib; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Rociletinib; T790M; epidermal growth factor receptor (EGFR); tyrosine kinase inhibitor