title: New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?
abstract: Recently, the development of the third-generation epidermal growth factor receptor-small molecule inhibitor (EGFR-TKI) rociletinib had failed. In this review, the wide-ranging aspects of the evolution of EGFR-TKIs were collected, with a special focus on rociletinib. The influence of different oncogenic mutations on EGFR activity was also discussed. Resistance to the first (erlotinib, gefitinib)- and second (afatinib)-generation EGFR-TKIs provided the rationale behind the development of the third-generation inhibitors (rociletinib, osimertinib). On the basis of these data, a comparison of their efficacy on the different mutated EGFRs and the respective resistance mechanisms is further reported. Moreover, the evolution and results of the clinical trials of rociletinib (TIGER trials) are compared with the trials on osimertinib, another third-generation EGFR-TKI that now has been granted US Food and Drug Administration approval. The reasons behind the arrest in the further development of rociletinib are put in the perspective of future drug development.
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Nele
authors: N
authors: Van Der Steen
authors: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors: Chiara
authors: C
authors: Caparello
authors: Phase I - Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Edegem.
authors: Christian
authors: C
authors: Rolfo
authors: Center for Oncological Research, University of Antwerp, Wilrijk, Antwerp, Belgium.
authors: Patrick
authors: P
authors: Pauwels
authors: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Godefridus J
authors: GJ
authors: Peters
authors: Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy.
authors: Elisa
authors: E
authors: Giovannetti
keywords: EGFR; EGFR-TKI; NSCLC; rociletinib; targeted therapies