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EGFR Mutations Detected in Plasma Are Associated with Patient Outcomes in Erlotinib Plus Docetaxel-Treated Non-small Cell Lung Cancer  Philip C. Mack,

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Presentation on theme: "EGFR Mutations Detected in Plasma Are Associated with Patient Outcomes in Erlotinib Plus Docetaxel-Treated Non-small Cell Lung Cancer  Philip C. Mack,"— Presentation transcript:

1 EGFR Mutations Detected in Plasma Are Associated with Patient Outcomes in Erlotinib Plus Docetaxel-Treated Non-small Cell Lung Cancer  Philip C. Mack, PhD, William S. Holland, MS, Rebekah A. Burich, MS, Randeep Sangha, MD, Leslie J. Solis, MS, Yueju Li, MA, Laurel A. Beckett, PhD, Primo N. Lara, MD, Angela M. Davies, MD, David R. Gandara, MD  Journal of Thoracic Oncology  Volume 4, Issue 12, Pages (December 2009) DOI: /JTO.0b013e3181bbf239 Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 Scorpion-amplification refractory mutation system (ARMS) assay sensitivity. Non-small cell lung cancer (NSCLC) lines harboring epidermal growth factor receptor (EGFR) and KRAS mutations were serially diluted and analyzed by Scorpion-ARMS. A, Genomic DNA was extracted from H1975 cells (mutations at L858R and T790M), H1650 (del746–750 mutation in exon 19), and A549 cells (wild type [WT] EGFR). DNA from the EGFR-mutant cell lines was diluted with DNA from A549 at the following ratios: 0, 0.5, 0.33, 0.1, 0.01, and B, A dilution series for the KRAS codon 12 GGT→AGT using DNA from A549 cells and H460 cells (WT at codon 12). C, Comparison between Scorpion-ARMS and DNA sequencing for the L858R mutation. Journal of Thoracic Oncology 2009 4, DOI: ( /JTO.0b013e3181bbf239) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 Representative examples of patient specimens positive for EGFR or KRAS mutations. A, Two patients with E19del identified in both plasma and tumor DNA. Both patients had complete response to therapy. B, A patient specimen with de novo positivity for both E19del and T790M. C, A patient with a KRAS mutation identified in both plasma and tumor. Journal of Thoracic Oncology 2009 4, DOI: ( /JTO.0b013e3181bbf239) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

4 FIGURE 3 Relationship between mutation-positivity and patient response. Clinical response data, as determined using RECIST criteria, was available for 45 patients. Those positive for activating mutations (E19del or L858R) were significantly associated with response to therapy (p = ) (labeled green). Four specimens were positive for T790M mutations, two of which also contained activating mutations (labeled yellow), occurring in patients with SD. Two KRAS mutations were identified in patients with progressive disease (labeled red). Journal of Thoracic Oncology 2009 4, DOI: ( /JTO.0b013e3181bbf239) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

5 FIGURE 4 A, EGFR activating mutations correlate with enhanced progression-free survival (PFS). Kaplan-Meier plot showing PFS of 49 patients stratified by mutation type. Patients with EGFR activating mutations (E19del or L858R) had significantly improved PFS compared with patients with WT EGFR or those harboring a resistance mutation (T790M or KRAS). B, Overall survival by mutation type. Kaplan-Meier plot showing overall survival of 49 patients stratified by mutation type. Journal of Thoracic Oncology 2009 4, DOI: ( /JTO.0b013e3181bbf239) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

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