Pharmacotherapy targeting the EGFR oncogene in NSCLC

Expert Opinion on Pharmacotherapy

Volumn 15, Issue 16, 2014, Pages 2293-2305

  Landi, Lorenza ^a   Cappuzzo, Federico ^a  

^a Livorno Hospital   (Italy)

Author keywords

Cetuximab; EGFR; EGFR mutation; EGFR tyrosinekinase inhibitors

Indexed keywords

AFATINIB; ANTINEOPLASTIC AGENT; CARBOPLATIN; CETUXIMAB; CISPLATIN; DACOMITINIB; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; GEMCITABINE; MATUZUMAB; MONOCLONAL ANTIBODY; NECITUMUMAB; PEMETREXED; PROTEIN TYROSINE KINASE INHIBITOR; PROTEIN KINASE INHIBITOR;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; CANCER CHEMOTHERAPY; CANCER SURVIVAL; DRUG MECHANISM; GENE MUTATION; HEALTH CARE QUALITY; HUMAN; MAINTENANCE CHEMOTHERAPY; MOLECULARLY TARGETED THERAPY; NON SMALL CELL LUNG CANCER; ONCOGENE; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; REVIEW; ANTAGONISTS AND INHIBITORS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE; GENETICS; LUNG NEOPLASMS; METABOLISM; MUTATION;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG RESISTANCE, NEOPLASM; HUMANS; LUNG NEOPLASMS; MOLECULAR TARGETED THERAPY; MUTATION; PROTEIN KINASE INHIBITORS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84911486852     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2014.957179     Document Type: Review

References (91)

1. DeSantis C, Naishadham D, Jemal A, et al. Cancer statistics for African Americans, 2013. CA Cancer J Clin 2013;63:151-66
2. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med 2002;346:92-8
3. Govindan R, Ding L, Griffith M, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 2012;150:1121-34
4. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39
5. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500
6. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004;101:13306-11
7. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-6
8. Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18:378-81
9. Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010;2:62ra93
10. Dutt A, Ramos AH, Hammerman PS, et al. Inhibitor-sensitive FGFR1 amplification in human nonsmall cell lung cancer. PLoS One 2011;6:e20351
11. Hammerman PS, Sos ML, Ramos AH, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov 2011;1:78-89
12. Yamamoto H, Shigematsu H, Nomura M, et al. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 2008;68:6913-21
13. Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res 2012;18:1167-76
14. Cohen BD, Kiener PA, Green JM, et al. The relationship between human epidermal growth-like factor receptor expression and cellular transformation in NIH3T3 cells. J Biol Chem 1996;271:30897-903
15. Grandis JR, Sok JC. Signaling through the epidermal growth factor receptor during the development of malignancy. Pharmacol Ther 2004;102:37-46
16. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183-232
17. Normanno N, Bianco C, Strizzi L, et al. The ErbB receptors and their ligands in cancer: an overview. Curr Drug Targets 2005;6:243-57
18. Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006;24:5034-42
19. Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 2005;97:643-55
20. Suzuki S, Dobashi Y, Sakurai H, et al. Protein overexpression and gene amplification of epidermal growth factor receptor in non small cell lung carcinomas. An immunohistochemical and fluorescence in situ hybridization study. Cancer 2005;103(6):1265-73
21. National cancer institute of Canada clinical trials group. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-32
22. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo controlled, multicentre study (Iressa survival evaluation in lung cancer). Lancet 2005;366:1527-37
23. Qi WX, Shen Z, Lin F, et al. Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev 2012;13:5177-82
24. Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol 2004;22:777-84
25. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 2004;22:785-94
26. Tokumo M, Toyooka S, Kiura K, et al. The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res 2005;11:1167-73
27. Akerley W, Boucher KM, Bentz JS, et al. A phase II study of erlotinib as initial treatment for patients with stage IIIB-IV non-small cell lung cancer. J Thorac Oncol 2009;4:214-19
28. Hesketh Hesketh PJ, Chansky K, Wozniak AJ, et al. Southwest oncology group phase II trial (S0341) of erlotinib (OSI-774) in patients with advanced non-small cell lung cancer and a performance status of 2. J Thorac Oncol 2008;3:1026-31
29. Jackman DM, Yeap BY, Lindeman NI, et al. Phase II clinical trial of chemotherapy-naive patients < or = 70 years of age treated with erlotinib for advanced non-small-cell lung cancer. J Clin Oncol 2007;25:760-6
30. Giaccone Giaccone G, Gallegos Ruiz M, Le Chevalier T, et al. Erlotinib for front line treatment of advanced non-small cell lung cancer: a phase II study. Clin Cancer Res 2006;12:6049-55
31. Niho Niho S, Kubota K, Goto K, et al. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer: a phase II study. J Clin Oncol 2006;24:64-9
32. Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005;23:5892-9
33. Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007;25:1545-52
34. Gridelli C, Ciardiello F, Gallo C, et al. First-line erlotinib followed by second line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol 2012;30:3002-11
35. Lee SM, Khan I, Upadhyay S, et al. First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebocontrolled, phase 3 trial. Lancet Oncol 2012;13:1161-70
36. Crinò L, Cappuzzo F, Zatloukal P, et al. Gefitinib versus vinorelbine in chemotherapy-naive elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized, phase II study. J Clin Oncol 2008;26:4253-60
37. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010;11:521-9
38. Johnson BE, Kabbinavar F, Fehrenbacher L, et al. ATLAS: randomized, double-blind, placebocontrolled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 2013;31:3926-34
39. Takeda K, Hida T, Sato T, et al. Randomized phase III trial of platinumdoublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a west Japan thoracic oncology group trial (WJTOG0203). J Clin Oncol 2010;28:753-60
40. Zhang L, Ma S, Song X, et al. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomized phase 3 trial. Lancet Oncol 2012;13:466-75
41. Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol 2012;7:1807-14
42. Ciuleanu T, Stelmakh L, Cicenas S, et al. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomized multicentre, open-label, phase 3 study. Lancet 2012;13:300-8
43. Karampeazis A, Voutsina A, Souglakos J, et al. Pemetrexed versus erlotinib in pretreated patients with advanced nonsmall cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer 2013;119(15):2754-64
44. Garassino MC, Martelli O, Broggini M, et al. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol 2013;14(10):981-8
45. Okano Y, Ando M, Asami K, et al. Randomized phase III trial of erlotinib (E) versus docetaxel (D) as second-or third-line therapy in patients with advanced non-small cell lung cancer (NSCLC) who have wild-type or mutant epidermal growth factor receptor (EGFR): Docetaxel and Erlotinib Lung Cancer Trial (DELTA). 2013 ASCO Annual Meeting, Oral Abstract Session, Lung Cancer-Non-small Cell Metastatic. J Clin Oncol 2013;31(Suppl):abstract 8006
46. Lazzari C, Novello S, Barni S, et al. Randomized proteomic stratified phase III study of second-line erlotinib (E) versus chemotherapy (CT) in patients with inoperable non-small cell lung cancer (PROSE). 2013 ASCO Annual Meeting, Oral Abstract Session, Lung Cancer-Non-small Cell Metastatic. J Clin Oncol 2013. 31(Suppl):abstract LBA8005
47. Shepherd FA, Douillard J, Fukuoka M, et al. Comparison of gefitinib and docetaxel in patients with pretreated advanced non-small cell lung cancer (NSCLC): meta-analysis from four clinical trials. J Clin Oncol 2009;27(Suppl):S15
48. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57
49. Han JY, Park K, Kim SW, et al. Firstsignal: first-line single-agent Iressa versus gemcitabine and cisplatin trial in neversmokers with adenocarcinoma of the lung. J Clin Oncol 2012;30:1122-8
50. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-8
51. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8
52. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as firstline treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735-42
53. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutationpositive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46
54. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2012;31:3327-34
55. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for firstline treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014;15:213-22
56. Janjigian YY, Smit EF, Groen HJM, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR mutant lung cancer with and without T790M mutations. Cancer Discov 2014;4:1-10
57. Therasse P, Arbuck SG, Eisenhauer EA, et al. Rubinstein Let al. New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the united states, national cancer institute of Canada. J Natl Cancer Inst 2000;92:205-16
58. Chaft JE, Oxnard GR, Sima CS, et al. Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin Cancer Res 2011;17:6298-303
59. Yu HA, Sima CS, Huang J, et al. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2013;8:346-51
60. Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFRmutant lung cancers. Clin Cancer Res 2013;19:2240-7
61. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3:75ra26
62. Zhang Y, Li XY, Tang Y, et al. Rapid increase of serum neuron specific enolase level and tachyphylaxis of EGFR-tyrosine kinase inhibitor indicate small cell lung cancer transformation from EGFR positive lung adenocarcinoma Lung Cancer 2013;81:302-5
63. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73
64. Yun CH, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008;105:2070-5
65. Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008;27:4702-11
66. Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012;13:528-38
67. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: A phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or Both. J Clin Oncol 2013;31:3335-41
68. Jackman D, Pao W, Riely GJ, et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010;28:357-60
69. Sequist LV, Besse B, Lynch TJ, et al. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer. J Clin Oncol 2010;28:3076-83
70. Engelman JA, Zejnullahu K, Gale CM, et al. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res 2007;67:11924-32
71. Ramalingam S, Blackhall F, Krzakowski M, et al. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol 2012;30:3337-44
72. Ramalingam SS, Janne PA, Mok T, et al. Randomized, double-blinded study of dacomitinib, an irreversible pan-human epidermal growth factor receptor (HER) inhibitor, versus erlotinib for second-line/third-line therapy of locally advanced/metastatic non-small cell lung cancer (ARCHER 1009) [abstract 8018]. J Clin Oncol 2014;32:5s
73. Sequist LV, Soria JC, Gadgeel S, et al. First-in-human evaluation of CO-1686, an irreversible, highly selective tyrosine kinase inhibitor of mutations of EGFR (activating and T790M) [abstract 8010]. J Clin Oncol 2014;35:5s
74. Janne PA, Ramalingam SS, Yang JC-H, et al. Clinical activity of the mutantselective EGFR inhibitor AZD9291 in patients (pts) with EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) [abstract 8009]. J Clin Oncol 2014;35:5s
75. Kurai J, Chikumi H, Hashimoto K, et al. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res 2007;13:1552-61
76. Steiner P, Joynes C, Bassi R, et al. Tumor growth inhibition with cetuximab and chemotherapy in non-small cell lung cancer xenografts expressing wild-type and mutated epidermal growth factor receptor. Clin Cancer Res 2007;13:1540-51
77. Raben D, Helfrich B, Chan DC, et al. The effects of cetuximab alone and in combination with radiation and/or chemotherapy in lung cancer. Clin Cancer Res 2005;11:795-805
78. Belani CP, Schreeder MT, Steis RG, et al. Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. Cancer 2008;113:2512-17
79. Butts CA, Bodkin D, Middleman EL, et al. Randomized phase II study of gemcitabine plus cisplatin or carboplatin, with or without cetuximab, as first-line therapy for patients with advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2007;25:5777-84
80. Rosell R, Robinet G, Szczesna A, et al. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol 2008;19:362-9
81. Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009;373:1525-31
82. Lynch TJ, Patel T, Dreisbach L, et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 2010;28:911-17
83. Herbst RS, Kelly K, Chansky K, et al. Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-smallcell lung cancer: southwest oncology group study S0342. J Clin Oncol 2010;28:4747-54
84. Pirker R, Pereira JR, von Pawel J, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 2012;13:33-42
85. Vanhoefer U, Tewes M, Rojo F, et al. Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J Clin Oncol 2004;22:175-84
86. Kollmannsberger C, Schittenhelm M, Honecker F, et al. A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC). Ann Oncol 2006;17:1007-13
87. Schiller JH, von Pawel J, Schutt P, et al. Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer. J Thorac Oncol 2010;5:1977-85
88. Thatcher N, Hirsch FR, Luft AV, et al. SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (Gem-Cis) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus gem-cis alone in the first line treatment of patients with stage IV squamous nonsmall cell lung cancer (Sq-NSCLC) [abstract 8008]. J Clin Oncol 2014;B2:5S
89. Paz-Ares L, Mezger J, Ciuleanu T, et al. Randomized phase III trial (INSPIRE) of necitumumab plus cisplatin-pemetrexed versus cisplatin-pemetrexed alone as first line therapy in non-squamous NSCLC. J Thor Oncol 2013;8(Suppl 2):S139
90. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011;12:175-80
91. Cardarella S, Ortiz TM, Joshi VA, et al. The introduction of systematic genomic testing for patients with non-small-cell lung cancer. J Thorac Oncol 2012;7:1767-74