Molecular targeted drugs and biomarkers in NSCLC the evolving role of individualized therapy

Journal of Cancer

Volumn 4, Issue 9, 2014, Pages 736-754

  Domvri, Kalliopi ^a   Zarogoulidis, Paul ^a,b   Darwiche, Kaid ^b   Browning, Robert F ^c   Li, Qiang ^d   Francis Turner, J ^e   Kioumis, Ioannis ^a   Spyratos, Dionysios ^a   Porpodis, Konstantinos ^a   Papaiwannou, Antonis ^a   Tsiouda, Theodora ^f   Freitag, Lutz ^b   Zarogoulidis, Konstantinos ^a  

^a ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^b RUHRLANDKLINIK   (Germany)

^c WALTER REED ARMY MEDICAL CENTER   (United States)

^d SECOND MILITARY MEDICAL UNIVERSITY   (China)

^e Pulmonary Medicine Associates Sleep Center   (United States)

^f Anticancer Hospital   (Greece)

Author keywords

Maintenance; NSCLC; Pathways; Targeted treatment

Indexed keywords

AFATINIB; AFLIBERCEPT; AVE 1642; BEVACIZUMAB; CARBOPLATIN; CETUXIMAB; CISPLATIN; CIXUTUMUMAB; CRIZOTINIB; DACOMITINIB; DOCETAXEL; DUSIGITUMAB; ERLOTINIB; EVEROLIMUS; FIGITUMUMAB; GEFITINIB; GEMCITABINE; NAVELBINE; NERATINIB; PACLITAXEL; PAZOPANIB; PEMETREXED; RAPAMYCIN; ROBATUMUMAB; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TIVANTINIB; UNINDEXED DRUG; VANDETANIB;

ANTINEOPLASTIC ACTIVITY; CANCER COMBINATION CHEMOTHERAPY; CHEMORADIOTHERAPY; COST EFFECTIVENESS ANALYSIS; DISEASE SEVERITY; DRUG EFFICACY; GENE MUTATION; HUMAN; LUNG NON SMALL CELL CANCER; MAINTENANCE THERAPY; MONOTHERAPY; OVERALL SURVIVAL; PERSONALIZED MEDICINE; PROGRESSION FREE SURVIVAL; PROTO ONCOGENE; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SURVIVAL RATE; SURVIVAL TIME; TREATMENT RESPONSE;

EID: 84893524965     PISSN: None     EISSN: 18379664     Source Type: Journal    
DOI: 10.7150/jca.7734     Document Type: Review

References (217)

1. Fuster LM, Sandler AB. Select clinical trials of erlotinib (OSI-774) in non-small-cell lung cancer with emphasis on phase III outcomes. Clin Lung Cancer. 2004; 6 Suppl 1: S24-9.
2. Vijayalakshmi R, Krishnamurthy A. Targetable "driver" mutations in non small cell lung cancer. Indian J Surg Oncol. 2011; 2: 178-88. doi:10.1007/s13193-011-0108-0.
3. Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future. J Clin Oncol. 2005; 23: 3175-85. doi:10.1200/JCO.2005.10.462.
4. Vineis P, Airoldi L, Veglia F, Olgiati L, Pastorelli R, Autrup H, et al. Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study. BMJ. 2005; 330: 277. doi:10.1136/bmj.38327.648472.82.
5. Tardon A, Lee WJ, Delgado-Rodriguez M, Dosemeci M, Albanes D, Hoover R, et al. Leisure-time physical activity and lung cancer: a meta-analysis. Cancer Causes Control. 2005; 16: 389-97. doi:10.1007/s10552-004-5026-9.
6. Lee IM. Physical activity and cancer prevention--data from epidemiologic studies. Med Sci Sports Exerc. 2003; 35: 1823-7. doi:10.1249/01.MSS.0000093620.27893.23.
7. Boffetta P. Epidemiology of environmental and occupational cancer. Oncogene. 2004; 23: 6392-403. doi:10.1038/sj.onc.1207715.
8. Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004; 350: 351-60. doi:10.1056/NEJMoa031644.
9. Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005; 352: 2589-97. doi:10.1056/NEJMoa043623.
10. Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990; 323: 940-5. doi:10.1056/NEJM199010043231403.
11. Matsuda A, Yamaoka K, Tango T. Quality of life in advanced non-small cell lung cancer patients receiving palliative chemotherapy: A meta-analysis of randomized controlled trials. Exp Ther Med. 2012; 3: 134-40. doi:10.3892/etm.2011.368.
12. Chen AB, Cronin A, Weeks JC, Chrischilles EA, Malin J, Hayman JA, et al. Palliative Radiation Therapy Practice in Patients With Metastatic Non-Small-Cell Lung Cancer: A Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) Study. J Clin Oncol. 2013; 31: 558-64. doi:10.1200/JCO.2012.43.7954.
13. Stinchcombe TE, Morris DE, Lee CB, Moore DT, Hayes DN, Halle JS, et al. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer. J Thorac Oncol. 2008; 3: 250-7. doi:10.1097/JTO.0b013e3181653cf4.
14. Yoshida T, Yamada K, Azuma K, Kawahara A, Abe H, Hattori S, et al. Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer: a retrospective analysis. Med Oncol. 2013; 30: 349. doi:10.1007/s12032-012-0349-y.
15. Tran B, Dancey JE, Kamel-Reid S, McPherson JD, Bedard PL, Brown AM, et al. Cancer genomics: technology, discovery, and translation. J Clin Oncol. 2012; 30: 647-60. doi:10.1200/JCO.2011.39.2316.
16. Koh PK, Faivre-Finn C, Blackhall FH, De Ruysscher D. Targeted agents in non-small cell lung cancer (NSCLC): clinical developments and rationale for the combination with thoracic radiotherapy. Cancer Treat Rev. 2012; 38: 626-40. doi:10.1016/j.ctrv.2011.11.003.
17. Langer CJ, Mok T, Postmus PE. Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). Cancer Treat Rev. 2013; 39: 252-60. doi:10.1016/j.ctrv.2012.05.003.
18. Azzoli CG, Temin S, Giaccone G. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. J Oncol Pract. 2012; 8: 63-6. doi:10.1200/JOP.2011.000374.
19. Domvri K, Darwiche K., Zarogoulidis P., Zarogoulidis K. Following the crumbs: from tissue samples, to pharmacogenomics, to NSCLC therapy. Transl Lung Cancer Res. 2012. doi: 10.3978/j.issn.2218-6751.2012.12.06.
20. Lesko LJ, Atkinson AJ, Jr. Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol. 2001; 41: 347-66. doi:10.1146/annurev.pharmtox.41.1.347.
21. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353: 123-32. doi:10.1056/NEJMoa050753.
22. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006; 355: 2542-50. doi:10.1056/NEJMoa061884.
23. Cardarella S, Ortiz TM, Joshi VA, Butaney M, Jackman DM, Kwiatkowski DJ, et al. The introduction of systematic genomic testing for patients with non-small-cell lung cancer. J Thorac Oncol. 2012; 7: 1767-74. doi:10.1097/JTO.0b013e3182745bcb.
24. Zhan P, Qian Q, Yu LK. Prognostic value of COX-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Dis. 2013; 5: 40-7. doi:10.3978/j.issn.2072-1439.2013.01.02.
25. Ko E, Lee BB, Kim Y, Lee EJ, Cho EY, Han J, et al. Association of RASSF1A and p63 with Poor Recurrence-Free Survival in Node-Negative Stage I-II Non-Small Cell Lung Cancer. Clin Cancer Res. 2013; 19: 1204-12. doi:10.1158/1078-0432.CCR-12-2848.
26. Stevenson JP, Langer CJ, Somer RA, Evans TL, Rajagopalan K, Krieger K, et al. Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer. Cancer. 2012; 118: 5580-7. doi:10.1002/cncr.27576.
27. Hallqvist A, Bergman B, Nyman J. Health related quality of life in locally advanced NSCLC treated with high dose radiotherapy and concurrent chemotherapy or cetuximab--pooled results from two prospective clinical trials. Radiother Oncol. 2012; 104: 39-44. doi:10.1016/j.radonc.2012.05.006.
28. Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004; 350: 379-92. doi:10.1056/NEJMra035536.
29. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 2006; 441: 424-30. doi:10.1038/nature04869.
30. Ohsaki Y, Tanno S, Fujita Y, Toyoshima E, Fujiuchi S, Nishigaki Y, et al. Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep. 2000; 7: 603-7.
31. Janku F, Garrido-Laguna I, Petruzelka LB, Stewart DJ, Kurzrock R. Novel therapeutic targets in non-small cell lung cancer. J Thorac Oncol. 2011; 6: 1601-12. doi:10.1097/JTO.0b013e31822944b3.
32. Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, 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 randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012; 13: 300-8. doi:10.1016/S1470-2045(11)70385-0.
33. Kris MG, Natale RB, Herbst RS, Lynch TJ, Jr., Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003; 290: 2149-58. doi:10.1001/jama.290.16.2149.
34. Simon GR, Ruckdeschel JC, Williams C, Cantor A, Chiappori A, Rocha Lima CM, et al. Gefitinib (ZD1839) in previously treated advanced non-small-cell lung cancer: experience from a single institution. Cancer Control. 2003; 10: 388-95.
35. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003; 21: 2237-46. doi:10.1200/JCO.2003.10.038.
36. Gaafar RM, Surmont VF, Scagliotti GV, Van Klaveren RJ, Papamichael D, Welch JJ, et al. A double-blind, randomised, placebo-controlled phase III intergroup study of gefitinib in patients with advanced NSCLC, non-progressing after first line platinum-based chemotherapy (EORTC 08021/ILCP 01/03). Eur J Cancer. 2011; 47: 2331-40. doi:10.1016/j.ejca.2011.06.045.
37. Lin WC, Chiu CH, Liou JL, Chen YM, Perng RP, Tsai CM. Gefitinib as front-line treatment in Chinese patients with advanced non-small-cell lung cancer. Lung Cancer. 2006; 54: 193-9. doi:10.1016/j.lungcan.2006.07.013.
38. Reck M, Buchholz E, Romer KS, Krutzfeldt K, Gatzemeier U, Manegold C. Gefitinib monotherapy in chemotherapy-naive patients with inoperable stage III/IV non-small-cell lung cancer. Clin Lung Cancer. 2006; 7: 406-11.
39. Suzuki R, Hasegawa Y, Baba K, Saka H, Saito H, Taniguchi H, et al. A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer. Br J Cancer. 2006; 94: 1599-603. doi:10.1038/sj.bjc.6603159.
40. Wang MZ, Li LY, Wang SL, Zhang XT, Zhong W, Zhang L. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer. Chin Med J (Engl). 2006; 119: 63-8.
41. Govindan R, Natale R, Wade J, Herbst R, Krebs A, Reiling R, et al. Efficacy and safety of gefitinib in chemonaive patients with advanced non-small cell lung cancer treated in an Expanded Access Program. Lung Cancer. 2006; 53: 331-7. doi:10.1016/j.lungcan.2006.04.013.
42. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol. 2006; 24: 2549-56. doi:10.1200/JCO.2005.04.9866.
43. Niho S, Kubota K, Goto K, Yoh K, Ohmatsu H, Kakinuma R, 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. doi:10.1200/JCO.2005.02.5825.
44. Sanford M, Scott LJ. Gefitinib: a review of its use in the treatment of locally advanced/metastatic non-small cell lung cancer. Drugs. 2009; 69: 2303-28. doi:10.2165/10489100-000000000-00000.
45. Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, 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. doi:10.1016/S0140-6736(05)67625-8.
46. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, 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. doi:10.1200/JCO.2004.08.001.
47. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, 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. doi:10.1200/JCO.2004.07.215
48. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, 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. doi:10.1056/NEJMoa040938.
49. Sugio K, Uramoto H, Onitsuka T, Mizukami M, Ichiki Y, Sugaya M, et al. Prospective phase II study of gefitinib in non-small cell lung cancer with epidermal growth factor receptor gene mutations. Lung Cancer. 2009; 64: 314-8. doi:10.1016/j.lungcan.2008.09.010.
50. Yang CH, Yu CJ, Shih JY, Chang YC, Hu FC, Tsai MC, et al. Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol. 2008; 26: 2745-53. doi:10.1200/JCO.2007.15.6695.
51. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, 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. doi:10.1016/S1470-2045(09)70364-X.
52. Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011; 29: 2866-74. doi:10.1200/JCO.2010.33.4235.
53. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304: 1497-500. doi:10.1126/science.1099314.
54. Takano T, Ohe Y, Sakamoto H, Tsuta K, Matsuno Y, Tateishi U, et al. Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol. 2005; 23: 6829-37. doi:10.1200/JCO.2005.01.0793.
55. Sequist LV. First-generation epidermal growth factor receptor tyrosine kinase inhibitors in EGFR mutation: positive non-small cell lung cancer patients. J Thorac Oncol. 2008; 3: S143-5. doi:10.1097/JTO.0b013e318174e981.
56. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361: 947-57. doi:10.1056/NEJMoa0810699.
57. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362: 2380-8. doi:10.1056/NEJMoa0909530.
58. Thongprasert S, Duffield E, Saijo N, Wu YL, Yang JC, Chu DT, et al. Health-related quality-of-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS). J Thorac Oncol. 2011; 6: 1872-80. doi:10.1097/JTO.0b013e31822adaf7.
59. Chen G, Feng J, Zhou C, Wu YL, Liu XQ, Wang C, et al. Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol. doi:10.1093/annonc/mdt012.
60. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line 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. doi:10.1016/S1470-2045(11)70184-X.
61. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13: 239-46. doi:10.1016/S1470-2045(11)70393-X.
62. Pallis AG, Voutsina A, Kentepozidis N, Giassas S, Papakotoulas P, Agelaki S, et al. A phase II trial of erlotinib as front-line treatment in clinically selected patients with non-small-cell lung cancer. Clin Lung Cancer. 2012; 13: 129-35. doi:10.1016/j.cllc.2011.08.004.
63. Choi DR, Lee DH, Choi CM, Kim SW, Suh C, Lee JS. Erlotinib in first-line therapy for non-small cell lung cancer: a prospective phase II study. Anticancer Res. 2011; 31: 3457-62. doi:31/10/3457 [pii].
64. Ku GY, Haaland BA, de Lima Lopes G, Jr. Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: meta-analysis of phase III trials. Lung Cancer. 2011; 74: 469-73. doi:10.1016/j.lungcan.2011.04.008.
65. Gao G, Ren S, Li A, Xu J, Xu Q, Su C, et al. Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials. Int J Cancer. 2012; 131: E822-9. doi:10.1002/ijc.27396.
66. Kosaka T, Yamaki E, Mogi A, Kuwano H. Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in non-small-cell lung cancer. J Biomed Biotechnol. 2011; 2011: 165214. doi:10.1155/2011/165214.
67. Pietanza MC, Gadgeel SM, Dowlati A, Lynch TJ, Salgia R, Rowland KM, Jr., et al. Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012; 7: 856-65. doi:10.1097/JTO.0b013e31824c943f.
68. Carillio G, Montanino A, Costanzo R, Sandomenico C, Piccirillo MC, Di Maio M, et al. Cetuximab in non-small-cell lung cancer. Expert Rev Anticancer Ther. 2012; 12: 163-75. doi:10.1586/era.11.178.
69. Ibrahim EM, Abouelkhair KM, Al-Masri OA, Chaudry NC, Kazkaz GA. Cetuximab-based therapy is effective in chemotherapy-naive patients with advanced and metastatic non-small-cell lung cancer: a meta-analysis of randomized controlled trials. Lung. 2011; 189: 193-8. doi:10.1007/s00408-011-9286-3.
70. Yap TA, Vidal L, Adam J, Stephens P, Spicer J, Shaw H, et al. Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol. 2010; 28: 3965-72. doi:10.1200/JCO.2009.26.7278.
71. Murakami H, Tamura T, Takahashi T, Nokihara H, Naito T, Nakamura Y, et al. Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol. 2012; 69: 891-9. doi:10.1007/s00280-011-1738-1.
72. Metro G, Crino L. The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer. Expert Rev Anticancer Ther. 2011; 11: 673-82. doi:10.1586/era.11.34.
73. Hirsh V, Cadranel J, Cong XJ, Fairclough D, Finnern HW, Lorence RM, et al. Symptom and Quality of Life Benefit of Afatinib in Advanced Non-Small-Cell Lung Cancer Patients Previously Treated with Erlotinib or Gefitinib: Results of a Randomized Phase IIb/III Trial (LUX-Lung 1). J Thorac Oncol. 2013; 8: 229-37. doi:10.1097/JTO.0b013e3182773fce.
74. Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012; 13: 539-48. doi:10.1016/S1470-2045(12)70086-4.
75. Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, 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. doi:10.1016/S1470-2045(12)70087-6.
76. Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013. doi:10.1200/JCO.2012.44.2806.
77. Rossi A, Pasquale R, Esposito C, Normanno N. Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients? Cancer Treat Rev. 2012. doi:10.1016/j.ctrv.2012.09.001.
78. Lee JS, Scott C, Komaki R, Fossella FV, Dundas GS, McDonald S, et al. Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06. J Clin Oncol. 1996; 14: 1055-64.
79. Gandara DR, Chansky K, Albain KS, Leigh BR, Gaspar LE, Lara PN, Jr., et al. Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase II Southwest Oncology Group Study S9504. J Clin Oncol. 2003; 21: 2004-10. doi:10.1200/JCO.2003.04.197.
80. Choy H. Combination chemoradiotherapy with gemcitabine: potential applications. Oncology (Williston Park). 2000; 14: 20-5.
81. Komaki R, Scott C, Ettinger D, Lee JS, Fossella FV, Curran W, et al. Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group (RTOG) 92-04. Int J Radiat Oncol Biol Phys. 1997; 38: 149-55.
82. Komaki R, Scott C, Lee JS, Urtasun RC, Byhardt RW, Emami B, et al. Impact of adding concurrent chemotherapy to hyperfractionated radiotherapy for locally advanced non-small cell lung cancer (NSCLC): comparison of RTOG 83-11 and RTOG 91-06. American journal of clinical oncology. 1997; 20: 435-40.
83. Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999; 17: 2692-9.
84. Rothschild S, Bucher SE, Bernier J, Aebersold DM, Zouhair A, Ries G, et al. Gefitinib in combination with irradiation with or without cisplatin in patients with inoperable stage III non-small cell lung cancer: a phase I trial. International journal of radiation oncology, biology, physics. 2011; 80: 126-32. doi:10.1016/j.ijrobp.2010.01.048.
85. Ready N, Janne PA, Bogart J, Dipetrillo T, Garst J, Graziano S, et al. Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial. J Thorac Oncol. 2010; 5: 1382-90. doi:10.1097/JTO.0b013e3181eba657.
86. Center B, Petty WJ, Ayala D, Hinson WH, Lovato J, Capellari J, et al. A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer. J Thorac Oncol. 2010; 5: 69-74. doi:10.1097/JTO.0b013e3181c59a0e.
87. Wang J, Xia TY, Wang YJ, Li HQ, Li P, Wang JD, et al. Prospective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer. International journal of radiation oncology, biology, physics. 2011; 81: e59-65. doi:10.1016/j.ijrobp.2010.12.035.
88. Chang CC, Chi KH, Kao SJ, Hsu PS, Tsang YW, Chang HJ, et al. Upfront gefitinib/erlotinib treatment followed by concomitant radiotherapy for advanced lung cancer: a mono-institutional experience. Lung Cancer. 2011; 73: 189-94. doi:10.1016/j.lungcan.2010.12.007.
89. Imai H, Shukuya T, Takahashi T, Fujiwara S, Mori K, Ono A, et al. Comparison of the Time-to-response Between Radiotherapy and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors for Advanced Non-small Cell Lung Cancer with EGFR Mutation. Anticancer Res. 2013; 33: 3279-84.
90. Sequist LV, Besse B, Lynch TJ, Miller VA, Wong KK, Gitlitz B, 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. doi:10.1200/JCO.2009.27.9414.
91. Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, 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. doi:10.1200/JCO.2011.40.9433.
92. Patil N, Abba M, Allgayer H. Cetuximab and biomarkers in non-small-cell lung carcinoma. Biologics. 2012; 6: 221-31. doi:10.2147/BTT.S24217.
93. Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, et al. Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], 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. doi:10.1200/JCO.2007.13.0856.
94. Rosell R, Robinet G, Szczesna A, Ramlau R, Constenla M, Mennecier BC, 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. doi:10.1093/annonc/mdm474.
95. Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, 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: 911-7. doi:10.1200/JCO.2009.21.9618.
96. Khambata-Ford S, Harbison CT, Hart LL, Awad M, Xu LA, Horak CE, et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2010; 28: 918-27. doi:10.1200/JCO.2009.25.2890.
97. Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol. 2008; 26: 3351-7. doi:10.1200/JCO.2007.14.0111.
98. Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, et al. Prognostic factors in patients with advanced non-small cell lung cancer: data from the phase III FLEX study. Lung Cancer. 2012; 77: 376-82. doi:10.1016/j.lungcan.2012.03.010.
99. Hanna N, Lilenbaum R, Ansari R, Lynch T, Govindan R, Janne PA, et al. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol. 2006; 24: 5253-8. doi:10.1200/JCO.2006.08.2263.
100. Lin H, Jiang J, Liang X, Zhou X, Huang R. Chemotherapy with cetuximab or chemotherapy alone for untreated advanced non-small-cell lung cancer: a systematic review and meta-analysis. Lung Cancer. 2010; 70: 57-62. doi:10.1016/j.lungcan.2010.01.009.
101. Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D, Lifshits E, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer cell. 2010; 17: 77-88. doi:10.1016/j.ccr.2009.11.022.
102. Belalcazar A, Azana D, Perez CA, Raez LE, Santos ES. Targeting the Met pathway in lung cancer. Expert Rev Anticancer Ther. 2012; 12: 519-28. doi:10.1586/era.12.16.
103. Goldman JW, Laux I, Chai F, Savage RE, Ferrari D, Garmey EG, et al. Phase 1 dose-escalation trial evaluating the combination of the selective MET (mesenchymal-epithelial transition factor) inhibitor tivantinib (ARQ 197) plus erlotinib. Cancer. 2012; 118: 5903-11. doi:10.1002/cncr.27575.
104. Sequist LV, von Pawel J, Garmey EG, Akerley WL, Brugger W, Ferrari D, et al. Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol. 2011; 29: 3307-15. doi:10.1200/JCO.2010.34.0570.
105. Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, et al. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer. 2012; 13: 391-5. doi:10.1016/j.cllc.2012.01.003.
106. Chang JW, Liu HP, Hsieh MH, Fang YF, Hsieh MS, Hsieh JJ, et al. Increased epidermal growth factor receptor (EGFR) gene copy number is strongly associated with EGFR mutations and adenocarcinoma in non-small cell lung cancers: a chromogenic in situ hybridization study of 182 patients. Lung Cancer. 2008; 61: 328-39. doi:10.1016/j.lungcan.2008.01.009.
107. Sasaki H, Endo K, Okuda K, Kawano O, Kitahara N, Tanaka H, et al. Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer. J Cancer Res Clin Oncol. 2008; 134: 569-77. doi:10.1007/s00432-007-0320-z.
108. Suzuki Y, Orita M, Shiraishi M, Hayashi K, Sekiya T. Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene. 1990; 5: 1037-43.
109. Schiller JH, Adak S, Feins RH, Keller SM, Fry WA, Livingston RB, et al. Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy. J Clin Oncol. 2001; 19: 448-57.
110. Aviel-Ronen S, Blackhall FH, Shepherd FA, Tsao MS. K-ras mutations in non-small-cell lung carcinoma: a review. Clin Lung Cancer. 2006; 8: 30-8. doi:10.3816/CLC.2006.n.030.
111. Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008; 9: 962-72. doi:10.1016/S1470-2045(08)70206-7.
112. Califano R, Landi L, Cappuzzo F. Prognostic and predictive value of K-RAS mutations in non-small cell lung cancer. Drugs. 2012; 72 Suppl 1: 28-36. doi:10.2165/1163012-S0-000000000-00000.
113. Mao C, Qiu LX, Liao RY, Du FB, Ding H, Yang WC, et al. KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: a meta-analysis of 22 studies. Lung Cancer. 2010; 69: 272-8. doi:10.1016/j.lungcan.2009.11.020.
114. Cadranel J, Mauguen A, Faller M, Zalcman G, Buisine MP, Westeel V, et al. Impact of systematic EGFR and KRAS mutation evaluation on progression-free survival and overall survival in patients with advanced non-small-cell lung cancer treated by erlotinib in a French prospective cohort (ERMETIC project--part 2). J Thorac Oncol. 2012; 7: 1490-502. doi:10.1097/JTO.0b013e318265b2b5.
115. Papadimitrakopoulou V. Development of PI3K/AKT/mTOR pathway inhibitors and their application in personalized therapy for non-small-cell lung cancer. J Thorac Oncol. 2012; 7: 1315-26. doi:10.1097/JTO.0b013e31825493eb.
116. Gridelli C, Maione P, Rossi A. The potential role of mTOR inhibitors in non-small cell lung cancer. Oncologist. 2008; 13: 139-47. doi:10.1634/theoncologist.2007-0171.
117. Papadimitrakopoulou VA, Soria JC, Jappe A, Jehl V, Klimovsky J, Johnson BE. Everolimus and erlotinib as second- or third-line therapy in patients with advanced non-small-cell lung cancer. J Thorac Oncol. 2012; 7: 1594-601. doi:10.1097/JTO.0b013e3182614835.
118. Ramalingam SS, Owonikoko TK, Behera M, Subramanian J, Saba NF, Kono SA, et al. Phase II study of docetaxel in combination with everolimus for second- or third-line therapy of advanced non-small-cell lung cancer. J Thorac Oncol. 2013; 8: 369-72. doi:10.1097/JTO.0b013e318282709c.
119. Dong S, Zhang XC, Cheng H, Zhu JQ, Chen ZH, Zhang YF, et al. Everolimus synergizes with gefitinib in non-small-cell lung cancer cell lines resistant to epidermal growth factor receptor tyrosine kinase inhibitors. Cancer Chemother Pharmacol. 2012; 70: 707-16. doi:10.1007/s00280-012-1946-3.
120. Donev IS, Wang W, Yamada T, Li Q, Takeuchi S, Matsumoto K, et al. Transient PI3K inhibition induces apoptosis and overcomes HGF-mediated resistance to EGFR-TKIs in EGFR mutant lung cancer. Clin Cancer Res. 2011; 17: 2260-9. doi:10.1158/1078-0432.CCR-10-1993.
121. Heavey S, O'Byrne KJ, Gately K. Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC. Cancer Treat Rev. 2013. doi:10.1016/j.ctrv.2013.08.006.
122. Zhang Y, Ni HJ, Cheng DY. Prognostic value of phosphorylated mTOR/RPS6KB1 in non- small cell lung cancer. Asian Pac J Cancer Prev. 2013; 14: 3725-8.
123. Gridelli C, Solange P, Sgambato A, Casaluce F, Adjei AA, Ciardiello F. ALK inhibitors in the treatment of advanced NSCLC. Cancer Treat Rev. 2013. doi:10.1016/j.ctrv.2013.07.002.
124. Kimura H, Nakajima T, Takeuchi K, Soda M, Mano H, Iizasa T, et al. ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity. Lung Cancer. 2012; 75: 66-72. doi:10.1016/j.lungcan.2011.05.027.
125. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med. 2008; 359: 1367-80. doi:10.1056/NEJMra0802714.
126. Solomon B, Varella-Garcia M, Camidge DR. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J Thorac Oncol. 2009; 4: 1450-4. doi:10.1097/JTO.0b013e3181c4dedb.
127. Pilotto S, Peretti U, Novello S, Rossi G, Milella M, Giaj Levra M, et al. PROFILing non-small-cell lung cancer patients for treatment with crizotinib according to anaplastic lymphoma kinase abnormalities: translating science into medicine. Expert Opin Pharmacother. 2013; 14: 597-608. doi:10.1517/14656566.2013.778828.
128. Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012; 13: 1011-9. doi:10.1016/S1470-2045(12)70344-3.
129. Seto T, Kiura K, Nishio M, Nakagawa K, Maemondo M, Inoue A, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol. 2013; 14: 590-8. doi:10.1016/S1470-2045(13)70142-6.
130. Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011; 12: 1004-12. doi:10.1016/S1470-2045(11)70232-7.
131. Chen X, Zhou JY, Zhao J, Chen JJ, Ma SN. Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells. Anticancer Drugs. 2013. doi:10.1097/CAD.0000000000000011.
132. Sachdev D, Yee D. The IGF system and breast cancer. Endocrine-related cancer. 2001; 8: 197-209.
133. Pollak MN. Insulin-like growth factors and neoplasia. Novartis Foundation symposium. 2004; 262: 84-98; discussion -107, 265-8.
134. Morgillo F, Kim WY, Kim ES, Ciardiello F, Hong WK, Lee HY. Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res. 2007; 13: 2795-803. doi:10.1158/1078-0432.CCR-06-2077.
135. Choi YJ, Rho JK, Jeon BS, Choi SJ, Park SC, Lee SS, et al. Combined inhibition of IGFR enhances the effects of gefitinib in H1650: a lung cancer cell line with EGFR mutation and primary resistance to EGFR-TK inhibitors. Cancer Chemother Pharmacol. 2010; 66: 381-8. doi:10.1007/s00280-009-1174-7.
136. Weickhardt A, Doebele R, Oton A, Lettieri J, Maxson D, Reynolds M, et al. A phase I/II study of erlotinib in combination with the anti-insulin-like growth factor-1 receptor monoclonal antibody IMC-A12 (cixutumumab) in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2012; 7: 419-26. doi:10.1097/JTO.0b013e31823c5b11.
137. Goto Y, Sekine I, Tanioka M, Shibata T, Tanai C, Asahina H, et al. Figitumumab combined with carboplatin and paclitaxel in treatment-naive Japanese patients with advanced non-small cell lung cancer. Investigational new drugs. 2012; 30: 1548-56. doi:10.1007/s10637-011-9715-4.
138. Gualberto A, Hixon ML, Karp DD, Li D, Green S, Dolled-Filhart M, et al. Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab. Br J Cancer. 2011; 104: 68-74. doi:10.1038/sj.bjc.6605972.
139. Ramalingam SS, Spigel DR, Chen D, Steins MB, Engelman JA, Schneider CP, et al. Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer. J Clin Oncol. 2011; 29: 4574-80. doi:10.1200/JCO.2011.36.6799.
140. Pallis AG, Christofillakis C, Tselepatiotis E, Agelaki S, Vamvakas L, Souglakos J, et al. Sequential administration of docetaxel followed by maintenance gefitinib, as salvage treatment in patients with advanced NSCLC: a multicenter phase II trial. Lung Cancer. 2007; 55: 101-7. doi:10.1016/j.lungcan.2006.08.019.
141. Cufer T, Vrdoljak E, Gaafar R, Erensoy I, Pemberton K. Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer. Anticancer Drugs. 2006; 17: 401-9. doi:10.1097/01.cad.0000203381.99490.ab.
142. Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, et al. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008; 26: 4244-52. doi:10.1200/JCO.2007.15.0185
143. Sekine I, Ichinose Y, Nishiwaki Y, Yamamoto N, Tsuboi M, Nakagawa K, et al. Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel. Ann Oncol. 2009; 20: 1483-8. doi:10.1093/annonc/mdp031.
144. Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, et al. Randomized Phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010; 16: 1307-14. doi:10.1158/1078-0432.CCR-09-1903.
145. Morere JF, Brechot JM, Westeel V, Gounant V, Lebeau B, Vaylet F, et al. Randomized phase II trial of gefitinib or gemcitabine or docetaxel chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2 or 3 (IFCT-0301 study). Lung Cancer. 2010; 70: 301-7. doi:10.1016/j.lungcan.2010.03.003.
146. Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008; 372: 1809-18. doi:10.1016/S0140-6736(08)61758-4.
147. Douillard JY, Shepherd FA, Hirsh V, Mok T, Socinski MA, Gervais R, et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol. 2010; 28: 744-52. doi:10.1200/JCO.2009.24.3030.
148. Cromwell I, van der Hoek K, Melosky B, Peacock S. Erlotinib or docetaxel for second-line treatment of non-small cell lung cancer: a real-world cost-effectiveness analysis. J Thorac Oncol. 2011; 6: 2097-103. doi:10.1097/JTO.0b013e31822f657a.
149. Krawczyk P, Kowalski DM, Wojas-Krawczyk K, Mlak R, Jaskiewicz P, Kucharczyk T, et al. The qualification of docetaxel or erlotinib for second-line therapy should be based on clinical and molecular predictive factors. Chemotherapy. 2012; 58: 60-9. doi:10.1159/000336143.
150. Kim ST, Uhm JE, Lee J, Sun JM, Sohn I, Kim SW, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy. Lung Cancer. 2012; 75: 82-8. doi:10.1016/j.lungcan.2011.05.022.
151. Fan WC, Yu CJ, Tsai CM, Huang MS, Lai CL, Hsia TC, et al. Different efficacies of erlotinib and gefitinib in taiwanese patients with advanced non-small cell lung cancer: a retrospective multicenter study. J Thorac Oncol. 2011; 6: 148-55. doi:10.1097/JTO.0b013e3181f77b27.
152. Shao YY, Shau WY, Lin ZZ, Chen HM, Kuo R, Yang JC, et al. Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer. Eur J Cancer. 2013; 49: 106-14. doi:10.1016/j.ejca.2012.07.014.
153. Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, 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. doi:10.1200/JCO.2005.02.840.
154. Natale RB, Bodkin D, Govindan R, Sleckman BG, Rizvi NA, Capo A, et al. Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study. J Clin Oncol. 2009; 27: 2523-9. doi:10.1200/JCO.2008.18.6015.
155. Hong J, Kyung SY, Lee SP, Park JW, Jung SH, Lee JI, et al. Pemetrexed versus gefitinib versus erlotinib in previously treated patients with non-small cell lung cancer. Korean J Intern Med. 2010; 25: 294-300. doi:10.3904/kjim.2010.25.3.294.
156. Lee DH, Kim SW, Suh C, Yoon DH, Yi EJ, Lee JS. Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment. Ann Oncol. 2008; 19: 2039-42. doi:10.1093/annonc/mdn423.
157. Zhou ZT, Xu XH, Wei Q, Lu MQ, Wang J, Wen CH. Erlotinib in advanced non-small-cell lung cancer after gefitinib failure. Cancer Chemother Pharmacol. 2009; 64: 1123-7. doi:10.1007/s00280-009-0973-1.
158. Cho BC, Im CK, Park MS, Kim SK, Chang J, Park JP, et al. Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol. 2007; 25: 2528-33. doi:10.1200/JCO.2006.10.4166.
159. Wong MK, Lo AI, Lam B, Lam WK, Ip MS, Ho JC. Erlotinib as salvage treatment after failure to first-line gefitinib in non-small cell lung cancer. Cancer Chemother Pharmacol. 2010; 65: 1023-8. doi:10.1007/s00280-009-1107-5.
160. Tsujino K, Kawaguchi T, Kubo A, Aono N, Nakao K, Koh Y, et al. Response rate is associated with prolonged survival in patients with advanced non-small cell lung cancer treated with gefitinib or erlotinib. J Thorac Oncol. 2009; 4: 994-1001. doi:10.1097/JTO.0b013e3181a94a2f.
161. Gridelli C, Maione P, Castaldo V, Rossi A. Gefitinib in elderly and unfit patients affected by advanced non-small-cell lung cancer. Br J Cancer. 2003; 89: 1827-9. doi:10.1038/sj.bjc.6601387.
162. Cappuzzo F, Bartolini S, Ceresoli GL, Tamberi S, Spreafico A, Lombardo L, et al. Efficacy and tolerability of gefitinib in pretreated elderly patients with advanced non-small-cell lung cancer (NSCLC). Br J Cancer. 2004; 90: 82-6. doi:10.1038/sj.bjc.6601470.
163. Oshita F, Yamada K, Saito H, Noda K. Phase II study of nedaplatin and irinotecan followed by gefitinib for elderly patients with unresectable non-small cell lung cancer. Cancer Chemother Pharmacol. 2008; 62: 465-70. doi:10.1007/s00280-007-0626-1.
164. Simon GR, Extermann M, Chiappori A, Williams CC, Begum M, Kapoor R, et al. Phase 2 trial of docetaxel and gefitinib in the first-line treatment of patients with advanced nonsmall-cell lung cancer (NSCLC) who are 70 years of age or older. Cancer. 2008; 112: 2021-9. doi:10.1002/cncr.23360.
165. Stinchcombe TE, Buzkova P, Choksi J, Taylor M, Bakri K, Gillenwater H, et al. A phase I/II trial of weekly docetaxel and gefitinib in elderly patients with stage IIIB/IV non-small cell lung cancer. Lung Cancer. 2006; 52: 305-11. doi:10.1016/j.lungcan.2006.03.002.
166. Stinchcombe TE, Peterman AH, Lee CB, Moore DT, Beaumont JL, Bradford DS, et al. A randomized phase II trial of first-line treatment with gemcitabine, erlotinib, or gemcitabine and erlotinib in elderly patients (age >/=70 years) with stage IIIB/IV non-small cell lung cancer. J Thorac Oncol. 2011; 6: 1569-77. doi:10.1097/JTO.0b013e3182210430.
167. Crino L, Cappuzzo F, Zatloukal P, Reck M, Pesek M, Thompson JC, 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. doi:10.1200/JCO.2007.15.0672.
168. Maemondo M, Minegishi Y, Inoue A, Kobayashi K, Harada M, Okinaga S, et al. First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study. J Thorac Oncol. 2012; 7: 1417-22. doi:10.1097/JTO.0b013e318260de8b.
169. Ebi N, Semba H, Tokunaga SJ, Takayama K, Wataya H, Kuraki T, et al. A phase II trial of gefitinib monotherapy in chemotherapy-naive patients of 75 years or older with advanced non-small cell lung cancer. J Thorac Oncol. 2008; 3: 1166-71. doi:10.1097/JTO.0b013e318186a88d.
170. LeCaer H, Greillier L, Corre R, Jullian H, Crequit J, Falchero L, et al. A multicenter phase II randomized trial of gemcitabine followed by erlotinib at progression, versus the reverse sequence, in vulnerable elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0505 study). Lung Cancer. 2012; 77: 97-103. doi:10.1016/j.lungcan.2012.02.004.
171. Chen YM, Tsai CM, Fan WC, Shih JF, Liu SH, Wu CH, et al. Phase II randomized trial of erlotinib or vinorelbine in chemonaive, advanced, non-small cell lung cancer patients aged 70 years or older. J Thorac Oncol. 2012; 7: 412-8. doi:10.1097/JTO.0b013e31823a39e8.
172. LeCaer H, Barlesi F, Corre R, Jullian H, Bota S, Falchero L, et al. A multicentre phase II randomised trial of weekly docetaxel/gemcitabine followed by erlotinib on progression, vs the reverse sequence, in elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0504 study). Br J Cancer. 2011; 105: 1123-30. doi:10.1038/bjc.2011.331.
173. Rossi D, Dennetta D, Ugolini M, Catalano V, Alessandroni P, Giordani P, et al. Activity and safety of erlotinib as second- and third-line treatment in elderly patients with advanced non-small cell lung cancer: a phase II trial. Target Oncol. 2010; 5: 231-5. doi:10.1007/s11523-010-0163-4.
174. Wheatley-Price P, Ding K, Seymour L, Clark GM, Shepherd FA. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol. 2008; 26: 2350-7. doi:10.1200/JCO.2007.15.2280.
175. Vadakara J, Borghaei H. Personalized medicine and treatment approaches in non-small-cell lung carcinoma. Pharmgenomics Pers Med. 2012; 5: 113-23. doi:10.2147/PGPM.S24258.
176. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990; 82: 4-6.
177. Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat. 1995; 36: 127-37.
178. Niho S, Kunitoh H, Nokihara H, Horai T, Ichinose Y, Hida T, et al. Randomized phase II study of first-line carboplatin-paclitaxel with or without bevacizumab in Japanese patients with advanced non-squamous non-small-cell lung cancer. Lung Cancer. 2012; 76: 362-7. doi:10.1016/j.lungcan.2011.12.005.
179. Pallis AG, Syrigos KN. Targeting tumor neovasculature in non-small-cell lung cancer. Crit Rev Oncol Hematol. 2012. doi:10.1016/j.critrevonc.2012.10.003.
180. Braghiroli MI, Sabbaga J, Hoff PM. Bevacizumab: overview of the literature. Expert Rev Anticancer Ther. 2012; 12: 567-80. doi:10.1586/era.12.13.
181. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009; 27: 1227-34. doi:10.1200/JCO.2007.14.5466.
182. Takeda M, Okamoto I, Yamanaka T, Nakagawa K, Nakanishi Y. Impact of treatment with bevacizumab beyond disease progression: a randomized phase II study of docetaxel with or without bevacizumab after platinum-based chemotherapy plus bevacizumab in patients with advanced nonsquamous non-small cell lung cancer (WJOG 5910L). BMC Cancer. 2012; 12: 327. doi:10.1186/1471-2407-12-327.
183. Lind JS, Senan S, Smit EF. Pulmonary toxicity after bevacizumab and concurrent thoracic radiotherapy observed in a phase I study for inoperable stage III non-small-cell lung cancer. J Clin Oncol. 2012; 30: e104-8. doi:10.1200/JCO.2011.38.4552.
184. Leighl NB, Raez LE, Besse B, Rosen PJ, Barlesi F, Massarelli E, et al. A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum- and erlotinib-resistant adenocarcinoma of the lung. J Thorac Oncol. 2010; 5: 1054-9.
185. Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, et al. Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012; 30: 3640-7. doi:10.1200/JCO.2012.42.6932.
186. Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, et al. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012; 30: 2070-8. doi:10.1200/JCO.2011.39.2993.
187. Dingemans AM, Mellema WW, Groen HJ, van Wijk A, Burgers SA, Kunst PW, et al. A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non-Small Cell Lung Cancer with a KRAS Mutation. Clin Cancer Res. 2013; 19: 743-51. doi:10.1158/1078-0432.CCR-12-1779.
188. Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, et al. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012; 30: 3084-92. doi:10.1200/JCO.2011.39.7646.
189. Blumenschein GR, Jr., Kabbinavar F, Menon H, Mok TS, Stephenson J, Beck JT, et al. A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2011; 22: 2057-67. doi:10.1093/annonc/mdq731.
190. Scagliotti GV, Vynnychenko I, Park K, Ichinose Y, Kubota K, Blackhall F, et al. International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol. 2012; 30: 2829-36. doi:10.1200/JCO.2011.41.4987.
191. Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pesek M, et al. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol. 2007; 25: 4270-7. doi:10.1200/JCO.2006.10.5122.
192. Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer research. 2002; 62: 4645-55.
193. Tamura T, Minami H, Yamada Y, Yamamoto N, Shimoyama T, Murakami H, et al. A phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors. J Thorac Oncol. 2006; 1: 1002-9.
194. Kiura K, Nakagawa K, Shinkai T, Eguchi K, Ohe Y, Yamamoto N, et al. A randomized, double-blind, phase IIa dose-finding study of Vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer. J Thorac Oncol. 2008; 3: 386-93. doi:10.1097/JTO.0b013e318168d228.
195. Heymach JV, Paz-Ares L, De Braud F, Sebastian M, Stewart DJ, Eberhardt WE, et al. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2008; 26: 5407-15. doi:10.1200/JCO.2008.17.3138.
196. de Boer RH, Arrieta O, Yang CH, Gottfried M, Chan V, Raats J, et al. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2011; 29: 1067-74. doi:10.1200/JCO.2010.29.5717.
197. Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, et al. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011; 29: 1059-66. doi:10.1200/JCO.2010.28.5981.
198. Lee JS, Hirsh V, Park K, Qin S, Blajman CR, Perng RP, et al. Vandetanib Versus placebo in patients with advanced non-small-cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: a randomized, double-blind phase III trial (ZEPHYR). J Clin Oncol. 2012; 30: 1114-21. doi:10.1200/JCO.2011.36.1709.
199. Breathnach OS, Freidlin B, Conley B, Green MR, Johnson DH, Gandara DR, et al. Twenty-two years of phase III trials for patients with advanced non-small-cell lung cancer: sobering results. J Clin Oncol. 2001; 19: 1734-42.
200. Lara PN, Jr., Redman MW, Kelly K, Edelman MJ, Williamson SK, Crowley JJ, et al. Disease control rate at 8 weeks predicts clinical benefit in advanced non-small-cell lung cancer: results from Southwest Oncology Group randomized trials. J Clin Oncol. 2008; 26: 463-7. doi:10.1200/JCO.2007.13.0344.
201. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008; 26: 3543-51. doi:10.1200/JCO.2007.15.0375.
202. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010; 21: 1804-9. doi:10.1093/annonc/mdq020.
203. Joshi M, Jiang Y, Belani CP. Maintenance therapy for advanced non-small-cell lung cancer: switch versus continuation. Expert Opin Pharmacother. 2012; 13: 685-97. doi:10.1517/14656566.2012.668530.
204. Zhang J, Zhang W, Huang S, Li H, Li Y, Chen H, et al. Maintenance erlotinib improves clinical outcomes of unresectable advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials. Exp Ther Med. 2012; 4: 849-58. doi:10.3892/etm.2012.690.
205. Qi WX, Tang LN, He AN, Shen Z, Lin F, Yao Y. Erlotinib and pemetrexed as maintenance therapy for advanced non-small-cell lung cancer: a systematic review and indirect comparison. Curr Med Res Opin. 2012; 28: 643-50. doi:10.1185/03007995.2012.675880.
206. Lu S, Yu YF. Maintenance Therapy for NSCLC: Consensus and Controversy. Chin J Cancer Res. 2011; 23: 254-8. doi:10.1007/s11670-011-0254-5.
207. Kelly K, Chansky K, Gaspar LE, Albain KS, Jett J, Ung YC, et al. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008; 26: 2450-6. doi:10.1200/JCO.2007.14.4824.
208. Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C, 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 randomised phase 3 trial. Lancet Oncol. 2012; 13: 466-75. doi:10.1016/S1470-2045(12)70117-1.
209. Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, et al. 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. doi:10.1016/S1470-2045(10)70112-1.
210. Patel JD, Hensing TA, Rademaker A, Hart EM, Blum MG, Milton DT, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer. J Clin Oncol. 2009; 27: 3284-9. doi:10.1200/JCO.2008.20.8181.
211. Belani CP, Goss G, Blumenschein G, Jr. Recent clinical developments and rationale for combining targeted agents in non-small cell lung cancer (NSCLC). Cancer Treat Rev. 2012; 38: 173-84. doi:10.1016/j.ctrv.2011.05.009.
212. Naumov GN, Nilsson MB, Cascone T, Briggs A, Straume O, Akslen LA, et al. Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res. 2009; 15: 3484-94. doi:10.1158/1078-0432.CCR-08-2904.
213. Falchook GS, Naing A, Hong DS, Zinner R, Fu S, Piha-Paul SA, et al. Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer. Oncotarget. 2013; 4: 118-27. doi:763 [pii].
214. Wheler JJ, Tsimberidou AM, Falchook GS, Zinner RG, Hong DS, Fok JY, et al. Combining Erlotinib and Cetuximab is Associated with Activity in Patients with Non Small Cell Lung Cancer (including Squamous Cell Carcinomas) and Wild-Type EGFR or Resistant Mutations. Molecular cancer therapeutics. 2013;doi:10.1158/1535-7163.MCT-12-1208.
215. Boutsikou E, Kontakiotis T, Zarogoulidis P, Darwiche K, Eleptheriadou E, Porpodis K, et al. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer. Onco Targets Ther. 2013; 6: 125-34. doi:10.2147/OTT.S42245
216. Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, et al. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011; 377: 1846-54. doi:10.1016/S0140-6736(11)60545-X.
217. Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GRJr., Tsao A, et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer discovery. 2011; 1: 44-53. doi:10.1158/2159-8274.CD-10-0010.