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- Title
Co-Occurring Driver Genomic Alterations in Advanced Non-Small-Cell Lung Cancer (NSCLC): A Retrospective Analysis.
- Authors
Attili, Ilaria; Asnaghi, Riccardo; Vacirca, Davide; Adorisio, Riccardo; Rappa, Alessandra; Ranghiero, Alberto; Lombardi, Mariano; Corvaja, Carla; Fuorivia, Valeria; Carnevale Schianca, Ambra; Trillo Aliaga, Pamela; Spitaleri, Gianluca; Del Signore, Ester; Guarize, Juliana; Spaggiari, Lorenzo; Guerini-Rocco, Elena; Fusco, Nicola; de Marinis, Filippo; Passaro, Antonio
- Abstract
Background: Actionable driver mutations account for 40–50% of NSCLC cases, and their identification clearly affects treatment choices and outcomes. Conversely, non-actionable mutations are genetic alterations that do not currently have established treatment implications. Among co-occurring alterations, the identification of concurrent actionable genomic alterations is a rare event, potentially impacting prognosis and treatment outcomes. Methods: We retrospectively evaluated the prevalence and patterns of concurrent driver genomic alterations in a large series of NSCLCs to investigate their association with clinicopathological characteristics, to assess the prognosis of patients whose tumor harbors concurrent alterations in the genes of interest and to explore their potential therapeutic implications. Results: Co-occurring driver alterations were identified in 26 out of 1520 patients with at least one gene alteration (1.7%). Within these cases, the incidence of concurrent actionable gene alterations was 39% (0.7% of the overall cohort). Among compound actionable gene mutations, EGFR was the most frequently involved gene (70%). The most frequent association was EGFR mutations with ROS1 rearrangement. Front-line targeted treatments were the preferred approach in patients with compound actionable mutations, with dismal median PFS observed (6 months). Conclusions: Advances in genomic profiling technologies are facilitating the identification of concurrent mutations. In patients with concurrent actionable gene alterations, integrated molecular and clinical data should be used to guide treatment decisions, always considering rebiopsy at the moment of disease progression.
- Subjects
NON-small-cell lung carcinoma; PROTEIN-tyrosine kinase inhibitors; NUCLEOTIDE sequencing; TREATMENT effectiveness; GENETIC mutation
- Publication
Journal of Clinical Medicine, 2024, Vol 13, Issue 15, p4476
- ISSN
2077-0383
- Publication type
Article
- DOI
10.3390/jcm13154476