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14-08-2018 | Non-small cell lung cancer | Article

Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI?

Nature Reviews Clinical Oncology

Authors: Gonzalo Recondo, Francesco Facchinetti, Ken A. Olaussen, Benjamin Besse, Luc Friboulet

Publisher: Nature Publishing Group UK


The traditional approach to the treatment of patients with advanced-stage non-small-cell lung carcinoma (NSCLC) harbouring ALK rearrangements or EGFR mutations has been the sequential administration of therapies (sequential treatment approach), in which patients first receive first-generation tyrosine-kinase inhibitors (TKIs), which are eventually replaced by next-generation TKIs and/or chemotherapy upon disease progression, in a decision optionally guided by tumour molecular profiling. In the past few years, this strategy has been challenged by clinical evidence showing improved progression-free survival, improved intracranial disease control and a generally favourable toxicity profile when next-generation EGFR and ALK TKIs are used in the first-line setting. In this Review, we describe the existing preclinical and clinical evidence supporting both treatment strategies — the ‘historical’ sequential treatment strategy and the use of next-generation TKIs — as frontline therapies and discuss the suitability of both strategies for patients with EGFR-driven or ALK-driven NSCLC.

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