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Review
. 2016 Oct 6:9:6065-6074.
doi: 10.2147/OTT.S97644. eCollection 2016.

New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?

Nele Van Der Steen  1 , Chiara Caparello  2 , Christian Rolfo  3 , Patrick Pauwels  4 , Godefridus J Peters  1 , Elisa Giovannetti  5
Affiliations
Review

New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?

Nele Van Der Steen et al. Onco Targets Ther. .

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.

Keywords: EGFR; EGFR-TKI; NSCLC; rociletinib; targeted therapies.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Timeline of EGFR-small molecule inhibitors, which shows the development of different generations of EGFR-TKIs up to 2015. Abbreviations: EGFR-TKI, epidermal growth factor receptor-small molecule inhibitor; NSCLC, non-small-cell lung cancer; FDA, Food and Drug Administration.
See this image and copyright information in PMC

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