Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need

Version 1 : Received: 2 May 2023 / Approved: 3 May 2023 / Online: 3 May 2023 (09:29:08 CEST)

A peer-reviewed article of this Preprint also exists.

Pretelli, G.; Spagnolo, C.C.; Ciappina, G.; Santarpia, M.; Pasello, G. Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need. Int. J. Mol. Sci. 2023, 24, 8878. Pretelli, G.; Spagnolo, C.C.; Ciappina, G.; Santarpia, M.; Pasello, G. Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need. Int. J. Mol. Sci. 2023, 24, 8878.

Abstract

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

Keywords

Non-small cell lung cancer (NSCLC); EGFR; Tyrosine kinase inhibitors (TKIs); Uncommon mutation; Compound mutation; Intracranial activity; Immunotherapy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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