| Autor: |
Rafael Rosell, Trever Bivona, Petros Giannikopoulos, Mayumi Ono, Miquel Taron, Santiago Viteri, Rosario Garcia-Campelo, Enric Carcereny, Enriqueta Felip, Margarita Majem, Teresa Moran, Jia Wei, Bartomeu Massuti, Radj Gervais, Niki Karachaliou, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Ana Drozdowskyj, Miguel Angel Molina, Carlota Costa |
| Rok vydání: |
2023 |
| Popis: |
Purpose: Concomitant genetic alterations could account for transient clinical responses to tyrosine kinase inhibitors of the EGF receptor (EGFR) in patients harboring activating EGFR mutations.Experimental Design: We have evaluated the impact of pretreatment somatic EGFR T790M mutations, TP53 mutations, and Bcl-2 interacting mediator of cell death (BCL2L11, also known as BIM) mRNA expression in 95 patients with EGFR-mutant non–small-cell lung cancer (NSCLC) included in the EURTAC trial (trial registration: NCT00446225).Results: T790M mutations were detected in 65.26% of patients using our highly sensitive method based on laser microdissection and peptide-nucleic acid-clamping PCR, which can detect the mutation at an allelic dilution of 1 in 5,000. Progression-free survival (PFS) to erlotinib was 9.7 months for those with T790M mutations and 15.8 months for those without, whereas among patients receiving chemotherapy, it was 6 and 5.1 months, respectively (P < 0.0001). PFS to erlotinib was 12.9 months for those with high and 7.2 months for those with low/intermediate BCL2L11 expression levels, whereas among chemotherapy-treated patients, it was 5.8 and 5.5 months, respectively (P = 0.0003). Overall survival was 28.6 months for patients with high BCL2L11 expression and 22.1 months for those with low/intermediate BCL2L11 expression (P = 0.0364). Multivariate analyses showed that erlotinib was a marker of longer PFS (HR = 0.35; P = 0.0003), whereas high BCL2L11 expression was a marker of longer PFS (HR = 0.49; P = 0.0122) and overall survival (HR = 0.53; P = 0.0323).Conclusions: Low-level pretreatment T790M mutations can frequently be detected and can be used for customizing treatment with T790M-specific inhibitors. BCL2L11 mRNA expression is a biomarker of survival in EGFR-mutant NSCLC and can potentially be used for synthetic lethality therapies. Clin Cancer Res; 20(7); 2001–10. ©2014 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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