Molecular Analysis-Based Treatment Strategies for the Management of Non-small Cell Lung Cancer Howard West, MD, Rogerio Lilenbaum, MD, David Harpole,

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Molecular Analysis-Based Treatment Strategies for the Management of Non-small Cell Lung Cancer Howard West, MD, Rogerio Lilenbaum, MD, David Harpole, MD, Antoinette Wozniak, MD, Lecia Sequist, MD, MPH Journal of Thoracic Oncology Volume 4, Issue 9, Pages S1029-S1039 (September 2009) DOI: 10.1097/JTO.0b013e3181b27170 Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 A, SEM image of an array of microposts etched in silicon. B, SEM image of an NCI-H1650 lung cancer cell spiked into blood. It has been captured on a micropost that has been chemically functionalized with antibodies against EpCAM. Inset image shows the cell at high magnification. EpCAM, epithelial cell adhesion molecule; SEM, scanning electron micrograph. Part A is reproduced with permission from Sunitha Nagrath, PhD and part B is reproduced with permission from Macmillan Publishers Ltd: Nature 2007;450:1235–1239. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Kaplan-Meier curve estimates of survival probability from the International Adjuvant Lung Trial. A significant improvement in the 5-year survival rate with cisplatin-based adjuvant chemotherapy compared with observation (control) occurred in the ERCC1-negative but not ERCC1-positive subgroup (HR = 0.65 and p = 0.002 versus HR = 1.14 and p = 0.4). ERCC1, excision repair cross-complementing group; HR, hazard ratio; OS, overall survival. Reproduced with permission from N Engl J Med 2006;355:983–991. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 The phase II MADeIT trial selected chemotherapy regimens on the basis of tumor expression levels of ERCC1 and RRM1 in patients with advanced NSCLC. ERCC1, excision repair cross-complementing group 1; MADeIT, Molecular Analyses–Directed Individualized Therapy for Advanced NSCLC; NSCLC, non-small cell lung cancer; RRM1, ribonucleotide reductase subunit 1; RT-PCR, reverse-transcriptase polymerase chain reaction. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Kaplan-Meier OS curves for patients with nonsquamous and squamous histologies. In patients with nonsquamous histologies, cisplatin/pemetrexed significantly improved OS compared with cisplatin/gemcitabine (11.8 months versus 10.4 months; p = 0.005), whereas patients with squamous cell carcinoma derived significantly improved OS with cisplatin/gemcitabine compared with cisplatin/pemetrexed (10.8 months versus 9.4 months; p = 0.05). CG, cisplatin/gemcitabine; CP, cisplatin/pemetrexed; HR, hazard ratio; OS, overall survival; SCC, squamous cell carcinoma. Reproduced with permission from J Clin Oncol 2008;26:3543–3551. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 5 Kaplan-Meier survival curve estimates for the Duke Training Cohort from the lung metagene model and a model based on combined clinical variables. The lung metagene model more clearly stratifies high-risk and low-risk patients with respect to survival when compared with the clinical model. Reproduced with permission from N Engl J Med. 2006;355:570–580. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 6 Trial schema for the BATTLE trial. BATTLE, Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 7 Plot of best response of indicator lesions according to RECIST criteria in patients with BAC and patients with adenocarcinoma with BAC subtype who received erlotinib. BAC, bronchioloalveolar carcinoma; CISH, chromogenic in situ hybridization; EGFR, epidermal growth factor receptor; RECIST, Response Evaluation Criteria in Solid Tumors. Reproduced with permission from J Clin Oncol 2008;26:1472–1478. Journal of Thoracic Oncology 2009 4, S1029-S1039DOI: (10.1097/JTO.0b013e3181b27170) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions