Targeted therapy for non-small-cell lung cancer: Past, present and future

Expert Review of Anticancer Therapy

Volumn 13, Issue 6, 2013, Pages 745-758

  Forde, Patrick M ^a   Ettinger, David S ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

PD1; targeted therapy; VEGF

Indexed keywords

AFATINIB; AFLIBERCEPT; B RAF KINASE; BEVACIZUMAB; CARBOPLATIN; CEDIRANIB; CETUXIMAB; CISPLATIN; CRIZOTINIB; CYTOTOXIC AGENT; DABRAFENIB; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; GEMCITABINE; MOTESANIB; NAVELBINE; ONARTUZUMAB; PACLITAXEL; PEMETREXED; PLACEBO; PLATINUM COMPLEX; PROTEIN TYROSINE KINASE INHIBITOR; SORAFENIB; SUNITINIB; TIVANTINIB; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN;

ADVANCED CANCER; ALOPECIA; ANEMIA; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; DIARRHEA; DRUG ERUPTION; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG TARGETING; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; EPIGENETICS; FATIGUE; FEBRILE NEUTROPENIA; GENE MUTATION; HEAD AND NECK CANCER; HUMAN; LUNG LOBECTOMY; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; MAINTENANCE THERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROTOXICITY; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PROGRESSION FREE SURVIVAL; PROTEIN TRANSPORT; REVIEW; SURVIVAL TIME; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR VASCULARIZATION;

CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE, NEOPLASM; EPIGENESIS, GENETIC; HUMANS; LUNG NEOPLASMS; MOLECULAR TARGETED THERAPY; MUTATION; PROTEIN KINASE INHIBITORS; PROTEIN TRANSPORT; PYRAZOLES; PYRIDINES; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84879379247     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.13.47     Document Type: Review

References (96)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J. Clin. 62(1), 10-29 (2012).
2. Yano T, Haro A, Shikada Y, Maruyama R, Maehara Y. Non-small cell lung cancer in never smokers as a representative 'nonsmoking-associated lung cancer': epidemiology and clinical features. Int. J. Clin. Oncol. 16(4), 287-293 (2011).
3. Overholt RH. Primary carcinoma of the lung: early diagnosis and treatment by pneumonectomy. N. Engl. J. Med. 214, 93-100 (1936).
4. Longeval E, Klastersky J. Combination chemotherapy with cisplatin and etoposide in bronchogenic squamous cell carcinoma and adenocarcinoma. A study by the EORTC Lung Cancer Working Party (Belgium). Cancer 50(12), 2751-2756 (1982).
5. Ruckdeschel JC, Finkelstein DM, Ettinger DS et al. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J. Clin. Oncol. 4(1), 14-22 (1986). (Pubitemid 16155956)
6. Bonomi P, Kim K, Fairclough D et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J. Clin. Oncol. 18(3), 623-631 (2000). (Pubitemid 30078543)
7. Kelly K, Crowley J, Bunn PA Jr et al. Randomized Phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J. Clin. Oncol. 19(13), 3210-3218 (2001). (Pubitemid 32591438)
8. Schiller JH, Harrington D, Belani CP et al.; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N. Engl. J. Med. 346(2), 92-98 (2002). (Pubitemid 34438899)
9. Paccagnella A, Oniga F, Bearz A et al. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a Phase II-III study. J. Clin. Oncol. 24(4), 681-687 (2006). (Pubitemid 46630434)
10. Delbaldo C, Michiels S, Syz N, Soria JC, Le Chevalier T, Pignon JP. Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 292(4), 470-484 (2004). (Pubitemid 38988956)
11. Rusch V, Klimstra D, Venkatraman E, Pisters PW, Langenfeld J, Dmitrovsky E. Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor ? is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin. Cancer Res. 3(4), 515-522 (1997). (Pubitemid 27211827)
12. Fujino S, Enokibori T, Tezuka N et al. A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur. J. Cancer 32A(12), 2070-2074 (1996). (Pubitemid 26419455)
13. Hirsch FR, Varella-Garcia M, Bunn PA Jr et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J. Clin. Oncol. 21(20), 3798-3807 (2003). (Pubitemid 46606235)
14. Han W, Lo HW. Landscape of EGFR signaling network in human cancers: biology and therapeutic response in relation to receptor subcellular locations. Cancer Lett. 318(2), 124-134 (2012).
15. Ranson M, Hammond LA, Ferry D et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a Phase I trial. J. Clin. Oncol. 20(9), 2240-2250 (2002). (Pubitemid 34441651)
16. Ho C, Murray N, Laskin J, Melosky B, Anderson H, Bebb G. Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America. Lung Cancer 49(2), 225-231 (2005). (Pubitemid 40966751)
17. 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. 22(5), 777-784 (2004). (Pubitemid 41103588)
18. 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. 22(5), 785-794 (2004). (Pubitemid 41103589)
19. Kim ES, Hirsh V, Mok T et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised Phase III trial. Lancet 372(9652), 1809-1818 (2008).
20. Maruyama R, Nishiwaki Y, Tamura T 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. 26(26), 4244-4252 (2008).
21. Lee DH, Park K, Kim 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. 16(4), 1307-1314 (2010).
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 366(9496), 1527-1537 (2005). (Pubitemid 41540110)
23. Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al.; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med. 353(2), 123-132 (2005).
24. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361(10), 947-957 (2009).
25. Fukuoka M, Wu YL, Thongprasert S 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. 29(21), 2866-2874 (2011).
26. Mitsudomi T, Morita S, Yatabe Y et al.; West Japan Oncology Group. 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. 11(2), 121-128 (2010).
27. Maemondo M, Inoue A, Kobayashi K et al.; North-East Japan Study Group. Gefitinib or chemotherapy for non-smallcell lung cancer with mutated EGFR. N. Engl. J. Med. 362(25), 2380-2388 (2010).
28. Zhou C, Wu YL, Chen G 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. 12(8), 735-742 (2011).
29. Sun Y, Wu YL, Zhou CC et al. Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study. Lung Cancer 79(2), 143-150 (2013).
30. Rosell R, Carcereny E, Gervais R et al.; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. 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. 13(3), 239-246 (2012).
31. Chih-Hsin Yang J, Schuler MH, Yamamoto N et al. Lux-Lung 3: A randomized, open-label, Phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. Presented at: 2012 ASCO Annual Meeting. Chicago, IL, USA, 1-5 June 2012.
32. Pirker R, Pereira JR, Szczesna A et al.; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised Phase III trial. Lancet 373(9674), 1525-1531 (2009).
33. Gatzemeier U, von Pawel J, Vynnychenko I et al. First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: a subgroup analysis of data from the FLEX Phase 3 study. Lancet Oncol. 12(1), 30-37 (2011).
34. 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. 13(1), 33-42 (2012).
35. Lynch TJ, Patel T, Dreisbach L et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-smallcell lung cancer: results of the randomized multicenter Phase III trial BMS099. J. Clin. Oncol. 28(6), 911-917 (2010).
36. Fojo T, Grady C. How much is life worth: cetuximab, non-small cell lung cancer, and the $440 billion question. J. Natl Cancer Inst. 101(15), 1044-1048 (2009).
37. Zhan P, Wang J, Lv XJ et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J. Thorac. Oncol. 4(9), 1094-1103 (2009).
38. Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355(24), 2542-2550 (2006). (Pubitemid 44917502)
39. Johnson DH, Fehrenbacher L, Novotny WF et al. Randomized Phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-smallcell lung cancer. J. Clin. Oncol. 22(11), 2184-2191 (2004). (Pubitemid 41095154)
40. Reck M, von Pawel J, Zatloukal P 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. 27(8), 1227-1234 (2009).
41. Reck M, von Pawel J, Zatloukal P et al.; BO17704 Study Group. 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. 21(9), 1804-1809 (2010).
42. Kabbinavar FF, Miller VA, Johnson BE et al. Overall survival in ATLAS, a Phase IIIb trial comparing bevacizumab therapy with or without erlotinib after completion of chemotherapy with bevacizumab for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer. Presented at: 2010 ASCO Annual Meeting. Chicago, IL, USA, 4-8 June 2012.
43. Goss GD, Arnold A, Shepherd FA et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J. Clin. Oncol. 28(1), 49-55 (2010).
44. Paz-Ares LG, Biesma B, Heigener D et al.; NSCLC [Non-Small-Cell Lung Cancer] Research Experience Utilizing Sorafenib (NExUS) Investigators Study Group. 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. 30(25), 3084-3092 (2012).
45. Scagliotti GV, Krzakowski M, Szczesna A 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. 30(17), 2070-2078 (2012).
46. Herbst RS, Sun Y, Eberhardt WE et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, Phase 3 trial. Lancet Oncol. 11(7), 619-626 (2010).
47. de Boer RH, Arrieta Ó, Yang CH 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. 29(8), 1067-1074 (2011).
48. Lee JS, Hirsh V, Park K 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. 30(10), 1114-1121 (2012).
49. Scagliotti GV, Vynnychenko I, Park K 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. 30(23), 2829-2836 (2012).
50. Ramlau R, Gorbunova V, Ciuleanu TE 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. 30(29), 3640-3647 (2012).
51. Lara PN Jr, Douillard JY, Nakagawa K et al. Randomized Phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J. Clin. Oncol. 29(22), 2965-2971 (2011).
52. Soda M, Choi YL, Enomoto M et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153), 561-566 (2007). (Pubitemid 47206930)
53. Takeuchi K, Choi YL, Togashi Y et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistrybased diagnostic system for ALK-positive lung cancer. Clin. Cancer Res. 15(9), 3143-3149 (2009).
54. Shaw AT, Yeap BY, Mino-Kenudson M et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J. Clin. Oncol. 27(26), 4247-4253 (2009).
55. Zou HY, Li Q, Lee JH et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 67(9), 4408-4417 (2007). (Pubitemid 46815090)
56. Kwak EL, Bang YJ, Camidge DR et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363(18), 1693-1703 (2010).
57. Camidge DR, Bang YJ, Kwak EL 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. 13(10), 1011-1019 (2012).
58. Sun JM, Ahn MJ, Ahn JS et al. Chemotherapy for pulmonary large cell neuroendocrine carcinoma: similar to that for small cell lung cancer or non-small cell lung cancer? Lung Cancer 77(2), 365-370 (2012).
59. Shaw AT. Phase 3 randomized study of crizotinib versus pemetrexed or docetaxel chemotherapy in advanced, ALK-positive NSCLC (PROFILE 1007). Presented at: 2012 ESMO Annual Meeting. Vienna, Austria, 30 September 2012 ( Abstract LBA1).
60. Voena C, Chiarle R. The battle against ALK resistance: successes and setbacks. Expert Opin. Investig. Drugs 21(12), 1751-1754 (2012).
61. Bergethon K, Shaw AT, Ou SH et al. ROS1 rearrangements define a unique molecular class of lung cancers. J. Clin. Oncol. 30(8), 863-870 (2012).
62. Scagliotti GV, Parikh P, von Pawel J 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. 26(21), 3543-3551 (2008).
63. Ceppi P, Rapa I, Lo Iacono M et al. Expression and pharmacological inhibition of thymidylate synthase and Src kinase in nonsmall cell lung cancer. Int. J. Cancer 130(8), 1777-1786 (2012).
64. Gridelli C, de Marinis F, Di Maio M et al. Maintenance treatment of advanced non-small-cell lung cancer: results of an International Expert Panel meeting of the Italian association of thoracic oncology. Lung Cancer 76(3), 269-279 (2012).
65. Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, Phase 3 study. Lancet 374(9699), 1432-1440 (2009).
66. 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. 11(6), 521-529 (2010).
67. Brugger W, Triller N, Blasinska-Morawiec M et al. Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. J. Clin. Oncol. 29(31), 4113-4120 (2011).
68. Edelman MJ, Le Chevalier T, Soria JC. Maintenance therapy and advanced non-small-cell lung cancer: a skeptic's view. J. Thorac. Oncol. 7(9), 1331-1336 (2012).
69. Pao W, Hutchinson KE. Chipping away at the lung cancer genome. Nat. Med. 18(3), 349-351 (2012).
70. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med. 182(2), 459-465 (1995).
71. Wolchok J. How recent advances in immunotherapy are changing the standard of care for patients with metastatic melanoma. Ann. Oncol. 23(Suppl. 8), viii 15-21 (2012).
72. Lynch TJ, Bondarenko I, Luft A et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter Phase II study. J. Clin. Oncol. 30(17), 2046-2054 (2012).
73. Zhang X, Schwartz JC, Guo X et al. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity 20(3), 337-347 (2004). (Pubitemid 38388235)
74. Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8(8), 793-800 (2002).
75. Thompson RH, Kuntz SM, Leibovich BC et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 66(7), 3381-3385 (2006).
76. Topalian SL, Hodi FS, Brahmer JR et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366(26), 2443-2454 (2012).
77. Patnaik A, Mishra SS, Senapati SB, Patra SK, Tripathy K, Burma S. Primary intraosseous malignant peripheral nerve sheath tumor of spine with a giant paraspinal and retrospinal subcutaneous extension. Surg. Neurol. Int. 3, 157 (2012).
78. Brahmer JR, Tykodi SS, Chow LQ et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366(26), 2455-2465 (2012).
79. Jones PA, Baylin SB. The epigenomics of cancer. Cell 128(4), 683-692 (2007). (Pubitemid 46273572)
80. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349(21), 2042-2054 (2003). (Pubitemid 37448928)
81. Silverman LR, Demakos EP, Peterson BL et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J. Clin. Oncol. 20(10), 2429-2440 (2002). (Pubitemid 34525728)
82. Cameron EE, Bachman KE, Myöhänen S, Herman JG, Baylin SB. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 21(1), 103-107 (1999). (Pubitemid 29036293)
83. Brock MV, Hooker CM, Ota-Machida E et al. DNA methylation markers and early recurrence in stage I lung cancer. N. Engl. J. Med. 358(11), 1118-1128 (2008). (Pubitemid 351398486)
84. Juergens RA, Wrangle J, Vendetti FP et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov. 1(7), 598-607 (2011).
85. Takeuchi K, Soda M, Togashi Y et al. RET, ROS1 and ALK fusions in lung cancer. Nat. Med. 18(3), 378-381 (2012).
86. Kelly RJ, Carter C, Giaccone G. Personalizing therapy in an epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer using PF-00299804 and trastuzumab. J. Clin. Oncol. 28(28), e507-e510 (2010).
87. Marchetti A, Felicioni L, Malatesta S et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J. Clin. Oncol. 29(26), 3574-3579 (2011).
88. Paik PK, Arcila ME, Fara M et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J. Clin. Oncol. 29(15), 2046-2051 (2011).
89. Sequist LV, Heist RS, Shaw AT et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann. Oncol. 22(12), 2616-2624 (2011).
90. Beau-Faller M, Ruppert AM, Voegeli AC et al. MET gene copy number in non-small cell lung cancer: molecular analysis in a targeted tyrosine kinase inhibitor naive cohort. J. Thorac. Oncol. 3(4), 331-339 (2008). (Pubitemid 351489471)
91. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat. Rev. Cancer 12(2), 89-103 (2012).
92. Bean J, Brennan C, Shih JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl Acad. Sci. USA 104(52), 20932-20937 (2007).
93. Spigel DR, Ervin TJ, Ramlau R et al. Final efficacy results from OAM4558g, a randomized Phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC. Presented at: 2011 ASCO Annual Meeting. Chicago, IL, USA, 3-7 June 2011.
94. Spigel DR, Edelman MJ, Mok T et al. Treatment rationale study design for the metlung trial: a randomized, double-blind Phase III study of onartuzumab (MetMAb) in combination with erlotinib versus erlotinib alone in patients who have received standard chemotherapy for stage iiib or iv met-positive non-small-cell lung cancer. Clin. Lung Cancer 13(6), 500-504 (2012).
95. Ayoola A, Barochia A, Belani K, Belani CP. Primary and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: an update. Cancer Invest. 30(5), 433-446 (2012).
96. Janjigian YY, Groen HJ, Horn L et al. Activity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib. Presented at: 2012 ASCO Annual Meeting. Chicago, IL, USA, 1-5 June 2012.