title: Profile of rociletinib and its potential in the treatment of non-small-cell lung cancer.
abstract: Patients with non-small-cell lung cancer (NSCLC) harboring activating mutations inEGFRbenefit from treatment with EGFR small-molecule tyrosine-kinase inhibitors. However, the development of acquired resistance to EGFR inhibitors is universal and limits treatment efficacy. Over half of patients receiving first-generation EGFR inhibitors (erlotinib and gefitinib) develop resistance via the gatekeeperEGFRT790M (EGFRT790M) mutation, and therapies able to overcome T790M-mediated resistance have been an unmet need in NSCLC. Rociletinib (CO-1686) is a third-generation small-molecule EGFR inhibitor with potent activity againstEGFRT790Mcurrently in advanced clinical development in NSCLC. Early clinical data suggested significant activity inEGFR-mutant NSCLC harboring T790M alterations. However, important questions regarding side-effect profile, comparability to competitor compounds, acquired resistance, EGFR-therapy sequencing, and combination therapies remain. Here, we review the available preclinical and clinical data for rociletinib, highlight the comparison to other third-generation EGFR inhibitors, and discuss resistance implications and future directions in NSCLC.
authors.affiliation: Division of Hematology/Oncology, University of California Irvine, Irvine, CA.
authors.forename: Phu N
authors.initials: PN
authors.lastname: Tran
authors.affiliation: Angeles Clinic and Research Institute; Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Klempner
keywords: CO-1686; EGFR; T790M; lung cancer; resistance; rociletinib; tyrosine-kinase inhibitor