Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI?
Abstract
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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The T790M gatekeeper mutation caused disease progression in 60% of cases.
“in 60% of cases this was due to the acquisition of the T790M ‘gatekeeper mutation’34,35.”
From Advances in covalent drug discovery (2022) · cites this paper as [35]
Some cancers, especially NSCLC, are addicted to the hyperactive EGFR pathway.
“Some cancers especially NSCLC are addicted to the hyperactive EGFR pathway [183].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [183]
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References 150 · Cited by 321
- Authors
- Recondo, G., Facchinetti, F., Olaussen, K. A., Besse, B., & Friboulet, L.
- Affiliations
- Inserm (FR)
- Corresponding author
- Friboulet, Luc
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2018-08-14
- Volume
- 15
- Issue
- 11
- Pages
- 694-708
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W2887531179
- Cited by
- 321
- References
- 150
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 40 · 2023: 36 · 2022: 67 · 2021: 64 · 2020: 41 · 2019: 40 · 2018: 11
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Pfizer
- AstraZeneca
- Fondation Nelia et Amadeo Barletta
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, EGFR mutation, ALK rearrangement, tyrosine kinase inhibitors, first-line therapy, sequential therapy, progression-free survival, intracranial disease control, targeted therapy
- MeSH terms
- Anaplastic Lymphoma Kinase, Carcinoma, Non-Small-Cell Lung, Humans, Mutation, Gene Rearrangement, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors
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