Understanding the new genetics of responsiveness to epidermal growth factor receptor tyrosine kinase inhibitors

Oncologist

Volumn 12, Issue 2, 2007, Pages 211-220

  Toschi, Luca ^a   Cappuzzo, Federico ^a  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

Author keywords

Epidermal growth factor receptor; Gefitinib erlotinib; Non small cell lung cancer; Tyrosine kinase inhibitors

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEFITINIB; K RAS PROTEIN; PLACEBO;

BIOLOGY; CANCER GROWTH; CANCER PATIENT; CANCER THERAPY; CIGARETTE SMOKING; CLINICAL FEATURE; CLINICAL TRIAL; COMPREHENSION; DIARRHEA; DRUG EFFECT; DRUG SENSITIVITY; GENE MUTATION; GENE NUMBER; GENE OVEREXPRESSION; GENETICS; HUMAN; LUNG NON SMALL CELL CANCER; ONCOGENE K RAS; OPTIMAL DRUG DOSE; PREDICTOR VARIABLE; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROTEIN EXPRESSION; RASH; RETROSPECTIVE STUDY; REVIEW; SURVIVAL;

ANTINEOPLASTIC AGENTS; HUMANS; LUNG NEOPLASMS; MUTATION; PROTEIN KINASE INHIBITORS; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 33847068819     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.12-2-211     Document Type: Review

References (92)

1. Salomon DS, Brandt R, Ciardiello F et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183-232.
2. Arteaga C. Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Semin Oncol 2002;29:3-9.
3. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999;82:241-250.
4. Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000;19:6550-6565.
5. Bunn PA Jr, Franklin W. Epidermal growth factor receptor expression, signal pathway, and inhibitors in non-small cell lung cancer. Semin Oncol 2002;29(suppl 14):38-44.
6. Natale RB. Biologically targeted treatment of non-small-cell lung cancer: Focus on epidermal growth factor receptor. Clin Lung Cancer 2003;5(suppl 1):S11-S17.
7. Herbst RS, Maddox AM, Rothenberg ML et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well tolerated and has activity in non-small cell lung cancer and other solid tumors: Results of a phase I trial. J Clin Oncol 2002;20:3815-3825.
8. 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 2002;20:2240-2250.
9. Nakagawa K, Tamura T, Negoro S et al. Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa' ZD1839) in Japanese patients with solid malignant tumors. Ann Oncol 2003;14:922-930.
10. Baselga J, Rischin D, Ranson M et al. Phase I safety, pharmacokinetics, and pharmacodynamic trial of ZD 1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 2002;20:4292-4302.
11. Goss G, Hirte H, Miller WH Jr et al. A phase I study of oral ZD1839 given daily in solid tumors: IND.122, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group. Invest New Drugs 2005;23:147-155.
12. Knight LA, Di Nicolantonio F, Whitehouse P et al. The in vitro effect of gefitinib (Iressa) alone and in combination with cytotoxic chemotherapy on human solid tumours. BMC Cancer 2004;4:1-8.
13. Hidalgo M, Siu LL, Nemunaitis J et al. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 2001;19:3267-3279.
14. Giaccone G. Her1/EGFR-targeted agents: Predicting the future for patients with unpredictable outcomes to therapy. Ann Oncol 2005;16:538-548.
15. 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) [published correction appears in J Clin Oncol 22:4811]. J Clin Oncol 2003;21:2237-2246.
16. Kris MG, Natale RB, Herbst RS 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.
17. Perez-Soler R, Chachoua A, Huberman M et al. Final results of a phase II study of erlotinib (Tarceva) monotherapy in patients with advanced non-small cell lung cancer following failure of platinum based chemotherapy. Lung Cancer 2003;41(suppl 2):S246.
18. Giaccone G, Herbst RS, Manegold C et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial - INTACT 1. J Clin Oncol 2004;22:777-784.
19. Herbst RS, Giaccone G, Schiller JH et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial - INTACT 2. J Clin Oncol 2004;22:785-794.
20. Gatzemeier U, Pluzanska A, Szczesna A et al. Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2004;22(suppl):617s:7010a.
21. Herbst RS, Prager D, Hermann R et al. TRIBUTE - A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005;23:5892-5899.
22. Thatcher N, Chang A, Parikh P et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005;366:1527-1537.
23. Shepherd FA, Pereira J, Ciuleanu TE et al. Erlotinib in previously treated non-small cell lung cancer. N Engl J Med 2005;353:123-132.
24. Lee DH, Han JY, Lee HG et al. Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers. Clin Cancer Res 2005;11:3032-3037.
25. Bailey LR, Kris M, Wolf M et al. Tumor EGFR membrane staining is not clinically relevant for predicting response in patients receiving gefitinib ('Iressa', ZD1839) monotherapy for pretreated advanced non-small-cell lung cancer: IDEAL 1 and 2. Proc Am Assoc Cancer Res 2003;44:1362 LB-170a.
26. Cappuzzo F, Gregorc V, Rossi E et al. Gefitinib in pretreated non-small-cell lung cancer (NSCLC): Analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. J Clin Oncol 2003;21:2658-2663.
27. Miller VA, Zakowski M, Riely GJ et al. EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma: Results of a prospective phase II trial. Proc Am Soc Clin Oncol 2006;24:324s:7003a.
28. Villaflor VM, Buckingham L, Gale M et al. EGFR mutations (muts), IHC and FISH status, and chromosome 7 gene copy number combined with pAkt expression as potential predictors of survival in non-small cell lung cancer (NSCLC) patients (pts) treated with gefitinib (GEF). J Clin Oncol 2006;24(suppl):18s:7182a.
29. Tsao MS, Sakurada A, Cutz JC et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005;353:133-144.
30. Cappuzzo F, Hirsch FR, Rossi E et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small cell lung cancer. J Natl Cancer Inst 2005;97:643-655.
31. Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-2139.
32. Paez JG, Janne PA, Lee JC et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004;304:1497-1500.
33. Pao W, Miller V, Zakowski M et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306 -13311.
34. Pham D, Kris MG, Riely GJ et al. Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas. J Clin Oncol 2006;24:1700-1704.
35. Marchetti A, Felicioni L, Buttitta F. Assessing EGFR mutations. N Engl J Med 2006;354:526-528.
36. Pao W, Miller VA, Politi KA et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:1-11.
37. Kobayashi S, Boggon TJ, Dayaram T et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-792.
38. Greulich H, Chen TH, Feng W et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med 2005;2:e313.
39. Kosaka T, Yatabe Y, Endoh H et al. Mutations of the epidermal growth factor receptor gene in lung cancer: Biological and clinical implications. Cancer Res 2004;64:8919-8923.
40. Bell DW, Gore I, Okimoto RA et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005;37:1315-1316.
41. Shigematsu H, Gazdar AF. Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer 2006;15:118:257-262.
42. Han SW, Kim TY, Hwang PG et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2005;23:2493-2501.
43. Kim KS, Jeong JY, Kim YC et al. Predictors of the response to gefitinib in refractory non-small cell lung cancer. Clin Cancer Res 2005;11:2244-2251.
44. Takano T, Ohe Y, Sakamoto H 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;23:6829-6837.
45. Cortes-Funes H, Gomez C, Rosell R et al. Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small cell lung cancer patients. Ann Oncol 2005;16:1081-1086.
46. Villaflor VM, Buckingham L, Gale M et al. EGFR mutations and pAKT expression as potential predictors of gefitinib efficacy in non-small cell lung cancer (NSCLC) patients (pts). J Clin Oncol 2005;23(suppl):639s:7077a.
47. Chou TY, Chiu CH, Li LH et al. Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer. Clin Cancer Res 2005;11:3750-3757.
48. Taron M, Ichinose Y, Rosell R et al. Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res 2005;11:5878-5885.
49. Mu XL, Li LY, Zhang XT et al. Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in Chinese patients with non-small cell lung cancer. Clin Cancer Res 2005;11:4289-4294.
50. Zhang XT, Li LY,MuXL et al. The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer. Ann Oncol 2005;16:1334-1342.
51. Mitsudomi T, Kosaka T, Endoh H et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment inpatients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 2005;23:2513-2520.
52. Paz-Ares L, Sanchez JM, García-Velasco A et al. A prospective phase II trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients (p) with mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR). J Clin Oncol 2006;24(suppl):18s:7020a.
53. Inoue A, Suzuki T, Fukuhara T et al. Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 2006;24:3340-3346.
54. Okamoto I, Kashii T, Urata Y et al. EGFR mutation-based phase II multicenter trial of gefitinib in advanced non-small cell lung cancer (NSCLC) patients (pts): Results of West Japan Thoracic Oncology Group trial (WJ-TOG0403). J Clin Oncol 2006;24(suppl):382s:7073.
55. Sutani A, Nagai Y, Udagawa K et al. Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp. J Clin Oncol 2006;24(suppl):383s:7076a.
56. Sunaga N, Yanagitani N, Kaira K et al. Phase II study of the efficacy of gefitinib in patients with non-small cell lung cancer with the EGFR mutations. J Clin Oncol 2006;24(suppl):18s:7183a.
57. Asahina H, Yamazaki K, Kinoshita I et al. Phase II study of gefitinib as a first-line therapy for advanced non-small cell lung cancers with epidermal growth factor receptor (EGFR) gene mutations. J Clin Oncol 2006;24(suppl):18s: 13014a.
58. Bell DW, Lynch TJ, Haserlat SM et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: Molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005;23:8081-8092.
59. Eberhard DA, Johnson BE, Amler LC et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005;23:5900-5909.
60. Gatzemeier U, Heller A, Foernzler D et al. Exploratory analyses EGFR, kRAS mutations and other molecular markers in tumors of NSCLC patients (pts) treated with chemotherapy +/- erlotinib (TALENT) J Clin Oncol 2005;23(suppl):16s:7028a.
61. Shigematsu H, Lin L, Takahashi T et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005;97:339-346.
62. Riely GJ, Pao W, Pham D et al. Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 2006;12:839-844.
63. Jackman DM, Yeap BY, Sequist LV et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res 2006;12:3908-3914.
64. Hirsch FR, Franklin WA, McCoy J et al. Predicting clinical benefit from EGFR TKIs: Not all EGFR mutations are equal. J Clin Oncol 2006;24(suppl):18s: 7072a.
65. Hirsch FR, Varella-Garcia M, Bunn PA et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small cell lung cancer. J Clin Oncol 2006;24:5034-5042.
66. Hirsch FR, Varella-Garcia M, McCoy J et al. Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: A Southwest Oncology Group Study. J Clin Oncol 2005;23:6838-6845.
67. Dziadziuszko R, Witta SE, Cappuzzo F et al. Epidermal growth factor receptor messenger RNA expression, gene dosage, and gefitinib sensitivity in non-small cell lung cancer. Clin Cancer Res 2006;12:3078-3084.
68. Lenferink AE, Pinkas-Kramarski R, van de Poll ML et al. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J 1998;17:3385-3397.
69. Moasser MM, Basso A, Averbuch SD et al. The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 2001;61:7184-7188.
70. Moulder SL, Yakes FM, Muthuswamy SK et al. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res 2001;61:8887-8895.
71. Normanno N, Campiglio M, De LA et al. Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth. Ann Oncol 2002;13:65-72.
72. Anido J, Matar P, Albanell J et al. ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells. Clin Cancer Res 2003;9:1274-1283.
73. Hirata A, Hosoi F, Miyagawa M et al. HER2 overexpression increases sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, through inhibition of HER2/HER3 heterodimer formation in lung cancer cells. Cancer Res 2005;65:4253-4260.
74. Cappuzzo F, Varella-Garcia M, Shigematsu H et al. Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients. J Clin Oncol 2005;23:5007-5018.
75. Shigematsu H, Takahashi T, Nomura M et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005;65:1642-1646.
76. Stephens P, Hunter C, Bignell G et al. Lung cancer: Intragenic ERBB2 kinase mutations in tumours. Nature 2004;431:525-526.
77. Cappuzzo F, Bemis L, Varella-Garcia M. HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N Engl J Med 2006;354:2619-2621.
78. Wang SE, Narasanna A, Perez-Torres M et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 2006;10:25-38.
79. Han SW, Kim TY, Jeon YK et al. Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin Cancer Res 2006;15:12:2538-2544.
80. Ahrendt SA, Decker PA, Alawi EA et al. Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 2001;92:1525-1530.
81. Marchetti A, Martella C, Felicioni L et al. EGFR mutations in non-small-cell lung cancer: Analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 2005;23:857-865.
82. Rodenhuis S, Slebos RJ, Boot AJ et al. Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 1988;48:5738-5741.
83. Suzuki Y, Orita M, Shiraishi M et al. Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene 1990;5:1037-1043.
84. Nelson HH, Christiani DC, Mark EJ et al. Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. J Natl Cancer Inst 1999;91:2032-2038.
85. Broermann P, Junker K, Brandt BH et al. Trimodality treatment in Stage III nonsmall cell lung carcinoma: Prognostic impact of K-ras mutations after neoadjuvant therapy. Cancer 2002;94:2055-2062.
86. Grossi F, Loprevite M, Chiaramondia M et al. Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers. Eur J Cancer 2003;39:1242-1250.
87. Huncharek M, Muscat J, Geschwind JF. K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: A combined analysis of 881 cases. Carcinogenesis 1999;20:1507-1510.
88. Yokoyama T, Kondo M, Goto Y et al. EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification. Cancer Sci 2006;97:753-759.
89. Suzuki M, Shigematsu H, Iizasa T et al. Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer 2006;106:2200-2207.
90. Pao W, Wang TY, Riely GJ et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17.
91. Conde E, Angulo B, Tang M et al. Molecular context of the EGFR mutations: Evidence for the activation of mTOR/S6K signaling. Clin Cancer Res 2006;12:710-717.
92. Tsao M, Zhu C, Sakurada A et al. An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer. J Clin Oncol. 2006;24(suppl):18s:7005a.