Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC)

Cancer Treatment Reviews

Volumn 39, Issue 3, 2013, Pages 252-260

  Langer, Corey J ^a   Mok, Tony ^b   Postmus, Pieter E ^c  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

BRAF; Epidermal growth factor receptor; Multikinase inhibitor; Non small cell lung cancer; RAF MEK ERK; Targeted therapy; Third line therapy; Tyrosine kinase inhibitor; Vascular endothelial growth factor receptor

Indexed keywords

5 (2,4 DIHYDROXY 5 ISOPROPYLPHENYL) 4 (4 MORPHOLINOMETHYLPHENYL) 3 ISOXAZOLECARBOXYLIC ACID ETHYLAMIDE; AFATINIB; AGO 1376; ANAPLASTIC LYMPHOMA KINASE; ANTINEOPLASTIC AGENT; APATINIB; AXITINIB; BASIC FIBROBLAST GROWTH FACTOR RECEPTOR; BEVACIZUMAB; BEXAROTENE; CRIZOTINIB; DOCETAXEL; ERLOTINIB; FIBROBLAST GROWTH FACTOR 2; GEFITINIB; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; HEAT SHOCK PROTEIN 90; MITOGEN ACTIVATED PROTEIN KINASE; PAZOPANIB; PEMETREXED; PLATELET DERIVED GROWTH FACTOR BB; RAF PROTEIN; SORAFENIB; SUNITINIB; TIVANTINIB; UNCLASSIFIED DRUG; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 2;

ADVANCED CANCER; ANOREXIA; ASTHENIA; AUTOPHOSPHORYLATION; CANCER CHEMOTHERAPY; CANCER RECURRENCE; CANCER RESISTANCE; CANCER STAGING; CELL PROLIFERATION; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; COMPETITIVE INHIBITION; CONJUNCTIVITIS; CONTINUOUS INFUSION; DIARRHEA; DISEASE ASSOCIATION; DRUG DOSE REDUCTION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ERUPTION; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; EXON; FATIGUE; GENETIC POLYMORPHISM; HEART ATRIUM FLUTTER; HUMAN; HYPERTENSION; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; MONOTHERAPY; MUTATIONAL ANALYSIS; NAUSEA AND VOMITING; NIGHT BLINDNESS; NONHUMAN; OVERALL SURVIVAL; POINT MUTATION; PROGRESSION FREE SURVIVAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN STABILITY; PROTEIN TARGETING; QUALITY OF LIFE; REVIEW; STOMATITIS; TREATMENT DURATION; TUMOR VOLUME; VISUAL DISORDER; WILD TYPE;

EID: 84873991616     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.05.003     Document Type: Review

References (119)

1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). non-small cell lung cancer. National Comprehensive Cancer, Network 2012.v2; 2012.
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOSCAN 2008 v. 1.2, Cancer incidence and mortality Worldwide: IARC CancerBase No. 10 [Internet].Lyon, France: International Agency for Research on Cancer. <>; 2010 [accessed 16.01.2012. http://www.globocan.iarc.fr.
3. Doll R., Gray R., Hafner B., Peto R. Mortality in relation to smoking: 22years' observations on female British doctors. Br Med J 1980, 280:967-971.
4. Doll R., Peto R. Mortality in relation to smoking: 20years' observations on male British doctors. Br Med J 1976, 2:1525-1536.
5. Janerich D.T., Thompson W.D., Varela L.R., et al. Lung cancer and exposure to tobacco smoke in the household. N Engl J Med 1990, 323:632-636.
6. Wald N.J., Nanchahal K., Thompson S.G., Cuckle H.S. Does breathing other people's tobacco smoke cause lung cancer?. Br Med J (Clin Res Ed) 1986, 293:1217-1222.
7. Turner M.C., Krewski D., Chen Y., Pope C.A., Gapstur S., Thun M.J. Radon and lung cancer in the American Cancer Society cohort. Cancer Epidemiol Biomarkers Prev 2011, 20:438-448.
8. van Dillen T., Dekkers F., Bijwaard H., Kreuzer M., Grosche B. Lung cancer from radon: a two-stage model analysis of the WISMUT Cohort, 1955-1998. Radiat Res 2011, 175:119-130.
9. Omenn G.S., Merchant J., Boatman E., et al. Contribution of environmental fibers to respiratory cancer. Environ Health Perspect 1986, 70:51-56.
10. Heintz N.H., Janssen-Heininger Y.M., Mossman B.T. Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways. Am J Respir Cell Mol Biol 2010, 42:133-139.
11. Boiselle P.M., Ernst A., Karp D.D. Lung cancer detection in the 21st century: potential contributions and challenges of emerging technologies. AJR Am J Roentgenol 2000, 175:1215-1221.
12. Aberle D.R., Adams A.M., Berg C.D., et al. Reduced lung cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011, 365:395-409. National Lung Screening Trial Research Team.
13. Bonomi P.D. Implications of key trials in advanced nonsmall cell lung cancer. Cancer 2010, 116:1155-1164.
14. Zhou C., Wu Y.L., 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 2011, 12:735-742.
15. Gerber D.E., Minna J.D. ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time. Cancer Cell 2010, 18:548-551.
16. Burris H.A. Shortcomings of current therapies for non-small-cell lung cancer: unmet medical needs. Oncogene 2009, 28(Suppl. 1):S4-S13.
17. Okamoto I., Mitsudomi T., Nakagawa K., Fukuoka M. The emerging role of epidermal growth factor receptor (EGFR) inhibitors in first-line treatment for patients with advanced non-small cell lung cancer positive for EGFR mutations. Ther Adv Med Oncol 2010, 2:301-307.
18. Syrigos K.N., Saif M.W., Karapanagiotou E.M., Oikonomopoulos G., De Marinis F. The need for third-line treatment in non-small cell lung cancer: an overview of new options. Anticancer Res 2011, 31:649-659.
19. Hait W.N., Hambley T.W. Targeted cancer therapeutics. Cancer Res 2009, 69:1263-1267.
20. Ballas M.S., Chachoua A. Rationale for targeting VEGF, FGF, and PDGF for the treatment of NSCLC. Onco Targets Ther 2011, 4:43-58.
21. Gazdar A.F. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 2009, 28(suppl 1):S24-S31.
22. Hirsch F.R., Varella-Garcia M., Cappuzzo F. Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer. Oncogene 2009, 28(suppl 1):S32-S37.
23. Ray M., Salgia R., Vokes E.E. The role of EGFR inhibition in the treatment of non-small cell lung cancer. Oncologist 2009, 14:1116-1130.
24. Fukuoka M., Wu Y.L., 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 2011, 29:2866-2874.
25. Pirker R., Pereira J.R., 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, 373:1525-1531. FLEX Study Team.
26. Inukai M., Toyooka S., Ito S., et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 2006, 66:7854-7858.
27. Pao W., Miller V.A., Politi K.A., 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.
28. Kobayashi S., Boggon T.J., Dayaram T., et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005, 352:786-792.
29. Balak M.N., Gong Y., Riely G.J., et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 2006, 12:6494-6501.
30. Bean J., Riely G.J., Balak M., et al. Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 2008, 14:7519-7525.
31. Costa D.B., Halmos B., Kumar A., et al. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med 2007, 4:1669-1679.
32. Engelman J.A., Zejnullahu K., Mitsudomi T., et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316:1039-1043.
33. Bean J., Brennan C., Shih J.Y., et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Nat Acad Sci USA 2007, 104:20932-20937.
34. Yano D., Wang W., Li Q., et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res 2008, 68:9479-9487.
35. Turke A.B., Zejnullahu K., Wu Y.L., et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010, 17:77-88.
36. Hanahan D., Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996, 86:353-364.
37. Ohta Y., Endo Y., Tanaka M., et al. Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer. Clin Cancer Res 1996, 2:1411-1416.
38. Yuan A., Yu C.J., Chen W.J., et al. Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer. Int J Cancer 2000, 89:475-483.
39. Masago K., Fujita S., Kim Y.H., et al. Effect of vascular endothelial growth factor polymorphisms on survival in advanced-stage non-small-cell lung cancer. Cancer Sci 2009, 100:1917-1922.
40. Guan X., Yin M., Wei Q., et al. Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy. BMC Cancer 2010, 10:431.
41. Gollob J.A., Wilhelm S., Carter C., Kelley S.L. Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol 2006, 33:392-406.
42. McCubrey J.A., Steelman L.S., Chappell W.H., et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007, 1773:1263-1284.
43. 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 2011, 29:3574-3579.
44. Boehm S., Rothermundt C., Hess D., Joerger M. Antiangiogenic drugs in oncology: a focus on drug safety and the elderly - a mini-review. Gerontology 2010, 56:303-309.
45. Langer C.J. Roles of EGFR and KRAS mutations in the treatment of patients with non-small-cell lung cancer. P T 2011, 36:263-279.
46. Shigematsu H., Lin L., Takahashi T., et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Nat Cancer Inst 2005, 97:339-346.
47. Janku F., Stewart D.J., Kurzrock R. Targeted therapy in non-small-cell lung cancer-is it becoming a reality?. Nat Rev Clin Oncol 2010, 7:401-414.
48. Maloney A., Workman P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther 2002, 2:3-24.
49. Bagatell R., Whitesell L. Altered Hsp90 function in cancer: a unique therapeutic opportunity. Mol Cancer Ther 2004, 3:1021-1030.
50. Sos M.L., Michel K., Zander T., et al. Predicting drug susceptibility of non-small cell lung cancers based on genetic lesions. J Clin Invest 2009, 119:1727-1740.
51. Soda M., Choi Y.L., Enomoto M., et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007, 448:561-566.
52. Mano H. Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer. Cancer Sci 2008, 99:2349-2355.
53. Behrens C., Lin H.Y., Lee J.J., et al. Immunohistochemical expression of basic fibroblast growth factor and fibroblast growth factor receptors 1 and 2 in the pathogenesis of lung cancer. Clin Cancer Res 2008, 14:6014-6022.
54. Weiss J., Sos M.L., Seidel D., et al. Frequent and focal FGFR1 amplification associated with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010, 2. 62ra93.
55. Dutt A., Ramos A.H., Hammerman P.S., et al. Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer. PLoS One 2011, 6:e20351.
56. Sasaki H., Shitara M., Yokota K., et al. Increased FGFR1 copy number in lung squamous cell carcinomas. Mol Med Report 2012, 5:725-728.
57. Shepherd F.A., Rodrigues Pereira J., Ciuleanu T., et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005, 353:123-132.
58. Felip E., Gridelli C., Baas P., Rosell R., Stahel R. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010. Ann Oncol 2011, 22:1507-1519.
59. Pircher A., Ploner F., Popper H., Hilbe W. Rationale of a relaunch of gefitinib in Caucasian non-small cell lung cancer patients. Lung cancer 2010, 69:265-271.
60. Fukuoka M., Yano S., Giaccone G., 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). J Clin Oncol 2003, 21:2237-2246.
61. Kris M.G., Natale R.B., Herbst R.S., 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, 290:2149-2158.
62. Kim E.S., Hirsh V., Mok T., et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008, 372:1809-1818.
63. Douillard J.Y., Shepherd F.A., Hirsh V., 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, 28:744-752.
64. Choi Y.L., Takeuchi K., Soda M., et al. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res 2008, 68:4971-4976.
65. Kwak E.L., Bang Y.J., Camidge D.R., et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010, 363:1693-1703.
66. Shaw A.T., Yeap B.Y., Solomon B.J., 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, 12:1004-1012.
67. Crinò L., Kim D., Riely G.J., et al. Initial phase II results with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC): PROFILE 1005. J Clin Oncol 2011, 29. Abstract 7514.
68. Heymach J.V., Johnson B.E., Prager D., et al. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol 2007, 25:4270-4277.
69. Heymach J.V., Paz-Ares L., De Braud F., 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, 28:5407-5415.
70. Herbst R.S., Sun Y., Eberhardt W.E., 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 2010, 11:619-626.
71. de Boer R.H., Arrieta O., Yang C.H., 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, 29:1067-1074.
72. Natale R.B., Thongprasert S., Greco F.A., 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, 29:1059-1066.
73. Lee J., Hirsh V., Park K., et al. Vandetanib versus placebo in patients with advanced non-small cell lung cancer (NSCLC) after prior therapy with an EGFR tyrosine kinase inhibitor (TKI): a randomized, double-blind, phase III trial (ZEPHYR). J Clin Oncol 2010, 28:1-2. Abstract 7525.
74. Socinski M.A., Novello S., Brahmer J.R., et al. Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol 2008, 26:650-656.
75. Novello S., Scagliotti G.V., Rosell R., et al. Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Br J Cancer 2009, 101:1543-1548.
76. Scagliotti G.V., Krzakowski M., Szczesna A., et al. Sunitinib (SU) in combination with erlotinib (E) for the treatment of advanced/metastatic non-small cell lung cancer (NSCLC): a phase III study. Ann Oncol 2010, 21(Suppl. 8):Viii3. Abstract LBA6.
77. Sunitinib as maintenance therapy in treating patients with stage III or stage IV non-small cell lung cancer previously treated with combination chemotherapy. CALGB 30607. <>; [accessed 7.05.2012]. http://www.clinicaltrials.gov/ct2/show/NCT00693992?term=sunitinib+AND+nsclc&rank=10.
78. Schiller J.H., Larson T., Ou S.H., et al. Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study. J Clin Oncol 2009, 27:3836-3841.
79. Spicer J.F., Rudman S.M. EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992. Target Oncol 2010, 5:245-255.
80. Minkovsky N., Berezov A. BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors. Curr Opin Invest Drugs 2008, 9:1336-1346.
81. Miller V.A., Hirsh V., Cadranel J., et al. Phase IIB/III double-blind randomized trial of afatinib (BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2)+best supportive care (BSC) versus placebo+BSC in patients with NSCLC failing 1-2 lines of chemotherapy and erlotinib or gefitinib (LUX-Lung 1). Ann Oncol 2010, 21(Suppl. 8):viii1. Abstract LBA1.
82. A phase II trial of afatinib (BIBW 2992) in third-line treatment for patients with stage IIIB/IV adenocarcinoma of the lung harbouring wild-type epidermal growth factor receptor [EGFR]. <>; [accessed 7.04.2012]. http://www.clinicaltrials.gov/ct2/show/NCT01003899?term=third-line&cond=non+small+cell+lung+cancer&rank=22.
83. Tian S., Quan H., Xie C., et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci 2011, 102:1374-1380.
84. Mi Y.J., Liang Y.J., Huang H.B., et al. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res 2010, 70:7981-7991.
85. Apatinib in the treatment of advanced non-squamous non-small cell lung cancer. <>; [accessed 1502.2012]. http://www.clinicaltrials.gov/ct2/show/NCT01287962?term=apatinib+AND+lung+cancer&rank=1.
86. A study of apatinib in patients with advanced non-squamous and non-small cell lung cancer. <>; [accessed 15.02.2012]. http://www.clinicaltrials.gov/ct2/show/NCT01270386?cond=non-small+cell+lung+cancer&intr=apatinib&rank=1.
87. Eccles S.A., Massey A., Raynaud F.I., et al. NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res 2008, 68:2850-2860.
88. Samuel T.A., Sessa C., Britten C., et al. AUY922, a novel HSP90 inhibitor: final results of a first-in-human study in patients with advanced solid malignancies. J Clin Oncol 2010, 28. Abstract 2528.
89. Sessa C., Sharma S.K., Britten C.D., et al. A phase I dose escalation study of AUY922, a novel HSP90 inhibitor, in patients with advanced solid malignancies. J Clin Oncol 2009, 27. Abstract 3532.
90. A study of AUY922 in non-small-cell lung cancer patients who have received previous two lines of chemotherapy. <>; [accessed 30.04.2012]. http://www.clinicaltrials.gov/ct2/show/NCT01124864?term=AUY922+AND+lung+cancer&rank=2.
91. Keisner S.V., Shah S.R. Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs 2011, 71:443-454.
92. Hamberg P., Verweij J., Sleijfer S. (Pre-)clinical pharmacology and activity of pazopanib, a novel multikinase angiogenesis inhibitor. Oncologist 2010, 15:539-547.
93. Ulahannan S.V., Brahmer J.R. Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer. Cancer Invest 2011, 29:325-337.
94. Altorki N., Lane M.E., Bauer T., et al. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer. J Clin Oncol 2010, 28:3131-3137.
95. GW786034 in patients with non small cell lung cancer 3rd line. <>; [accessed 16.03.2012]. http://www.clinicaltrials.gov/ct2/show/NCT01049776?term=.+%28NCT01049776%29&rank=1.
96. Wilhelm S.M., Carter C., Tang L., et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004, 64:7099-7109.
97. Blumenschein G.R., Gatzemeier U., Fossella F., et al. Phase II, multicenter, uncontrolled trial of single-agent sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer. J Clin Oncol 2009, 27:4274-4280.
98. Schiller J.H., Lee J.W., Hanna N.H., Traynor A.M., Carbone D.P. A randomized discontinuation phase II study of sorafenib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens: E2501. J Clin Oncol 2008, 26. Abstract 8014.
99. A 3rd/4th line placebo-controlled trial of sorafenib in patients with predominantly nonsquamous non-small cell lung cancer NSCLC (MISSION). <>; [accessed 2.04.2012]. http://www.clinicaltrials.gov/ct2/show/NCT00863746?term=%28NCT00863746%29.&rank=1.
100. Eathiraj S., Palma R., Vockova E., et al. Discovery of a novel mode of protein kinase inhibition characterized by the mechanism of inhibition of human mesenchymal-epithelial transition factor (c-Met) protein autophosphorylation by ARQ 197. J Biol Chem 2011, 286:20666-20676.
101. Sequist L.V., von Pawel J., Garmey E.G., et al. Randomized phase II study of erlotinib plus tivantinib versus erlontinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol 2011, 29:3307-3315.
102. Sandler A., Schiller J.H., Hirsh V., et al. A phase III, randomized, double-blind, placebo-controlled study of erlotinib plus ARQ versus erlontinib plus placebo in previously treated subjects with locally advanced or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). J Clin Oncol 2011, 29(15S). Abstract TPS217.
103. ARQ 197 plus erlotinib versus placebo plus erlotinib for the treatment of non-squamous, non-small-cell lung cancer. <>; [accessed 22.03.2012]. http://www.clinicaltrials.gov/ct2/show/NCT01244191?term=tivantinib&rank=6.
104. Pennell N.A., Lynch T.J. Combined inhibition of the VEGFR and EGFR signaling pathways in the treatment of NSCLC. Oncologist 2009, 14:399-411.
105. Scagliotti G., Govindan R. Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer. Oncologist 2010, 15:436-446.
106. Sandler A., Gray R., Perry M.C., et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med 2006, 355:2542-2550.
107. Johnson D.H., Fehrenbacher L., Novotny W.F., 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-small cell lung cancer. J Clin Oncol 2004, 22:2184-2191.
108. Scagliotti G., Novello S., von Pawel J., et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small cell lung cancer. J Clin Oncol 2010, 28:1835-1842.
109. Gadgeel S.M., Woznak A., Edelman M.J. Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed I patients (pts) with recurrent non-small cell lung cancer (NSCLC). J Clin Oncol 2009, 27(15S). Abstract 319007.
110. Kim E.S., Herbst R.S., Wistuba I.I., et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Disc 2011, 1:44-53.
111. Smit E.F., Dingemans A.M.C., Thunnissen F.B., Hochstenback M.M., van Suylen R.J., Postmus P.E. Sorafenib in patients with advanced non-small cell lung cancer that harbor K-ras mutations: a brief report. J Thorac Oncol 2010, 5:719-720.
112. Dingemans AM, Mellema WW, Groen HJM, et al. A phase II study of sorafenib in patients with locally advanced and/or metastatic (stage IIIB or IV) non-small cell lung cancer (NSCLC) with a K-ras mutation. Paper presented at the 2011 European Multidisciplinary Cancer Congress of the European Society for Medical Oncology (ESMO); September 24-27, 2011. Abstract LBA 27.
113. Reck M., Hermes A., Tan E.H., Felip E., Klughammer B., Baselga J. Tissue sampling in lung cancer: a review in light of the MERIT experience. Lung cancer 2011, 74:1-6.
114. Girard N., Jacoulet P., Gainet M., et al. Third-line chemotherapy in advanced non-small cell lung cancer: identifying the candidates for routine practice. J Thorac Oncol 2009, 4:1544-1549.
115. Asahina H., Sekine I., Horinouchi H., et al. Retrospective analysis of third-line and fourth-line chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer 2012, 13:39-43.
116. Becker A., Crombag L., Heideman D.A., et al. Retreatment with erlotinib: regain of TKI sensitivity following a drug holiday for patients with NSCLC who originally responded to EGFR-TKI treatment. Eur J Cancer 2011, 47:2603-2606.
117. Lara P.N., Redman M.W., Kelly K., et al. Southwest Oncology Group. 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, 26:463-467.
118. Heist R.S., Christiani D. EGFR-targeted therapies in lung cancer: predictors of response and toxicity. Pharmacogenomics 2009, 10:59-68.
119. Wu J., Lu L.Y., Yu X. The role of BRCA1 in DNA damage response. Protein Cell 2010, 1:117-123.