The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations-The Lung Cancer Mutation Consortium (LCMC2).

Aisner DL, Sholl LM, Berry LD, Rossi MR, Chen H, Fujimoto J, Moreira AL, Ramalingam SS, Villaruz LC, Otterson GA, Haura E, Politi K, Glisson B, Cetnar J, Garon EB, Schiller J, Waqar SN, Sequist LV, Brahmer J, Shyr Y, Kugler K, Wistuba II, Johnson BE, Minna JD, Kris MG, Bunn PA, Kwiatkowski DJ, LCMC2 investigators
Clin Cancer Res. 2018 24 (5): 1038-1047

PMID: 29217530 · PMCID: PMC7008001 · DOI:10.1158/1078-0432.CCR-17-2289

Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC. The use of targeted therapies in patients with or p.V600E mutations, , or rearrangements, or amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver. Importantly, 60 patients with a history of smoking derived similar survival benefit from targeted therapy for alterations in //, when compared with 75 never smokers with the same alterations. In addition, coexisting mutations were associated with shorter survival among patients with , or alterations. Patients with adenocarcinoma of the lung and an oncogenic driver mutation treated with effective targeted therapy have a longer survival, regardless of prior smoking history. Molecular testing should be performed on all individuals with lung adenocarcinomas irrespective of clinical characteristics. Routine use of massively parallel sequencing enables detection of both targetable driver alterations and tumor suppressor gene and other alterations that have potential significance for therapy selection and as predictive markers for the efficacy of treatment. .

©2017 American Association for Cancer Research.

MeSH Terms (23)

Adenocarcinoma of Lung Adult Aged Aged, 80 and over Antineoplastic Agents Biomarkers, Tumor Carcinogenesis DNA Mutational Analysis Female High-Throughput Nucleotide Sequencing Humans Lung Neoplasms Male Middle Aged Molecular Targeted Therapy Mutation Prognosis Prospective Studies Smoking Survival Analysis Treatment Outcome Tumor Suppressor Protein p53 Young Adult

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