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Master of Public Health

The Impact of Smoking and TP53 mutations in lung adenocarcinoma patients with targetable mutations - the Lung Cancer Mutation Consortium (LCMC2).

AUTHORS

Aisner DL , Sholl LM , Berry L , Rossi M , Chen H , Fujimoto J , Moreira AL , Ramalingam S , Villaruz LC , Otterson GA , Haura EB , Politi K , Glisson BS , Cetnar J , Garon E , Schiller J , Waqar S , Sequist LV , Brahmer JR , Shyr Y , Kugler K , Wistuba II , Johnson BE , Minna JD , Kris MG , Bunn PA , Kwiatkowski DJ , . Clinical cancer research : an official journal of the American Association for Cancer Research. 2017 12 7; ().
  • NIHMSID: 9502500

ABSTRACT

PURPOSE 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. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients 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 immunohistochemistry. RESULTS The use of targeted therapies in patients with EGFR, ERBB2, or BRAF p.V600E mutations, ALK, ROS1 or RET rearrangements, or MET amplification was associated with a survival increment of 1.5 years compared to those with such mutations not receiving targeted therapy; and 1.0 year compared to those lacking a targetable driver. Importantly, 60 patients with a history of smoking derived similar survival benefit from targeted therapy for alterations in EGFR ALK/ROS1, when compared to 75 never smokers with the same alterations. In addition, co-existing TP53 mutations were associated with shorter survival among patients with EGFR, ALK, or ROS1 alterations. CONCLUSION 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.

PURPOSE 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. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients 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 immunohistochemistry. RESULTS The use of targeted therapies in patients with EGFR, ERBB2, or BRAF p.V600E mutations, ALK, ROS1 or RET rearrangements, or MET amplification was associated with a survival increment of 1.5 years compared to those with such mutations not receiving targeted therapy; and 1.0 year compared to those lacking a targetable driver. Importantly, 60 patients with a history of smoking derived similar survival benefit from targeted therapy for alterations in EGFR ALK/ROS1, when compared to 75 never smokers with the same alterations. In addition, co-existing TP53 mutations were associated with shorter survival among patients with EGFR, ALK, or ROS1 alterations. CONCLUSION 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.

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