The role of irreversible EGFR inhibitors in the treatment of non-small cell lung cancer: Overcoming resistance to reversible EGFR inhibitors

Cancer Investigation

Volumn 28, Issue 4, 2010, Pages 413-423

  Belani, Chandra P ^a  

^a PENN STATE CANCER INSTITUTE   (United States)

Author keywords

Epidermal growth factor receptor; HER2; HKI 272; Irreversible tyrosine kinase inhibitors BIBW 2992; Non small cell lung cancer; PF00299804

Indexed keywords

4 [3 CHLORO 4 (2 PYRIDINYLMETHOXY)ANILINO] 3 CYANO 6 (4 DIMETHYLAMINOCROTONAMIDO) 7 ETHOXYQUINOLINE; AV 412; CANERTINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; GEFITINIB; LAPATINIB; MP 412; N [4 (3 CHLORO 4 FLUOROANILINO) 7 (TETRAHYDRO 3 FURYLOXY) 6 QUINAZOLINYL] 4 DIMETHYLAMINO 2 BUTENAMIDE; PELITINIB; PF 299804; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CANCER CHEMOTHERAPY; CANCER RESEARCH; CLINICAL TRIAL; DRUG RESEARCH; ENZYME INHIBITION; GENE MUTATION; HUMAN; LUNG NON SMALL CELL CANCER; PRIORITY JOURNAL; REVIEW;

CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; HUMANS; LUNG NEOPLASMS; MORPHOLINES; MUTATION; PROTEIN KINASE INHIBITORS; QUINAZOLINES; QUINAZOLINONES; QUINOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 77950586775     PISSN: 07357907     EISSN: 15324192     Source Type: Journal    
DOI: 10.3109/07357901003631072     Document Type: Review

References (84)

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology(tm). Non-Small Cell Lung Cancer V. 2. Pennsylvania: NCCN, 2009.
2. Arriagada, R.; Bergman, B.; Dunant, A.; Le Chevalier, T.; Pignon, J.P.; Vansteenkiste, J. for the International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004, 350, 351-360. (Pubitemid 38101630)
3. Curran, W.; Scott, C.; Langer, C.; Komaki, R.; Lee, J.; Hauser, S.; Movsas, B.;Wasserman, T.; Rosenthal, S.; Byhardt, R.; Sause,W.; Cox, J. Phase III comparison of sequential vs. concurrent chemoradiation for patients (pts) with unresected stage-III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410. Proc Am Soc Clin Oncol 2000, 19, 484a.
4. Dillman, R.O.; Seagren, S.L.; Propert, K.J.; Guerra, J.; Eaton,W.L.; Perry, M.C.; Carey, R.W.; Frei, E.F. III; Green, M.R. 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, 940-945.
5. Winton, T.; Livingston, R.; Johnson, D.; Rigas, J.; Johnston, M.; Butts, C.; Cormier, Y.; Goss, G.; Inculet, R.; Vallieres, E.; Fry, W.; Bethune, D.; Ayoub, J.; Ding, K.; Seymour, L.; Graham, B.; Tsao, M.S.; Gandara, D.; Kesler, K.; Demmy, T.; Shepherd, F. for the National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small cell lung cancer. N Engl J Med 2005, 352, 2589-2597.
6. Sharma, S.V.; Bell, D.W.; Settleman, J.; Haber, D.A. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007, 7, 169-181.
7. Shepherd, F.A.; Pereira, J.R.; Ciuleanu, T.; Tan, E.H.; Hirsh, V.; Thongprasert, S.; Campos, D.; Maoleekoonpiroj, S.; Smylie, M.; Martins, R.; van Kooten, M.; Dediu, M.; Findlay, B.; Tu, D.; Johnston, D.; Bezjak, A.; Clark, G.; Santabarbara, P.; Seymour, L. Erlotinib in previously treated non-small cell lung cancer. N Engl J Med 2005, 353, 123-132.
8. Kris, M.G.; Natale, R.B.; Herbst, R.S.; Lynch, T.J., Jr.; Prager, D.; Belani, C.P.; Schiller, J.H.; Kelly, K.; Spiridonidis, H.; Sandler, A.; Albain, K.S.; Cella, D.; Wolf, M.K.; Averbuch, S.D.; Ochs, J.J.; Kay, A.C. 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. (Pubitemid 37432975)
9. Thatcher, N.; Chang, A.; Parikh, P.; Pereira, J.R.; Ciuleanu, T.; von Pawel, J.; Thongprasert, S.; Tan, E.H.; Pemberton, K.; Archer, V.; Carroll, K. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small cell lung cancer: results from a randomized, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005, 366, 1527-1537.
10. Kim, E.S.; Hirsh, V.; Mok, T.; Socinski, M.A.; Gervais, R.; Wu, Y.L.; Li, L.Y.;Watkins, C.L.; Sellers,M.V.; Lowe, E.S.; Sun, Y.; Liao, M.L.; Osterlind, K.; Reck, M.; Armour, A.A.; Shepherd, F.A.; Lippman, S.M.; Douillard, J.Y. Gefitinib versus docetaxel in previously treated non-small cell lung cancer (INTEREST): a randomized phase III trial. Lancet 2008, 372, 1809-1818.
11. Pao, W. Defining clinically relevant molecular subsets of lung cancer. Cancer Chemother Pharmacol 2006, 58(Suppl. 1), s11-s15.
12. Fukuoka, M.; Yano, S.; Giaccone, G.; Tamura, T.; Nakagawa, K.; Douillard, J.Y.; Nishiwaki, Y.; Vansteenkiste, J.; Kudoh, S.; Rischin, D.; Eek, R.; Horai, T.; Noda, K.; Takata, I.; Smit, E.; Averbuch, S.; Macleod, A.; Feyereislova, A.; Dong, R.P.; Baselga, J. Multiinstitutional 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, 2237-2246.
13. Bell, D.W.; Lynch, T.J.; Haserlat, S.M.; Harris, P.L.; Okimoto, R.A.; Brannigan, B.W.; Sgroi, D.C.; Muir, B.; Riemenschneider, M.J.; Iacona, R.B.; Krebs, A.D.; Johnson, D.H.; Giaccone, G.; Herbst, R.S.; Manegold, C.; Fukuoka, M.; Kris, M.G.; Baselga, J.; Ochs, J.S.; Haber, D.A. 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.
14. Lynch, T.J.; Bell, D.W.; Sordella, R.; Gurubhagavatula, S.; Okimoto, R.A.; Brannigan, B.W.; Harris, P.L.; Haserlat, S.M.; Supko, J.G.; Haluska, F.G.; Louis, D.N.; Christiani, D.C.; Settleman, J.; Haber, D.A. 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.
15. Mok, T.; Wu, Y.-L.; Thongprasert, S.; Yang, C.-H.; Chu, D.; Seijo, N.; Watkins, C.; Armour, A.; Fukuoka, M. Phase III, randomised, open-label, first-line study of gefitinib (G) vs. carboplatin/paclitaxel (C/P) in clinically selected patients (PTS) with advanced non-small cell lung cancer (NSCLC) (IPASS) (abstract no. LBA2). Ann Oncol 2008, 19 (Suppl. 8), viii1-viii4.
16. Paez, J.G.; Jänne, P.A.; Lee, J.C.; Tracy, S.; Greulich, H.; Gabriel, S.; Herman, P.; Kaye, F.J.; Lindeman, N.; Boggon, T.J.; Naoki, K.; Sasaki, H.; Fujii, Y.; Eck, M.J.; Sellers, W.R.; Johnson, B.E.; Meyerson, M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004, 304, 1497-1500.
17. Jang, T.W.; Oak, C.H.; Chang, H.K.; Suo, S.J.; Jung, M.H. EGFR and KRAS mutations in patients with adenocarcinoma of the lung. Korean J Intern Med 2009, 24, 48-54.
18. Kwak, E.L.; Sordella, R.; Bell, D.W.; Godin-Heymann, N.; Okimoto, R.A.; Brannigan, B.W.; Harris, P.L.; Driscoll, D.R.; Fidias, P.; Lynch, T.J.; Rabindran, S.K.; McGinnis, J.P.; Wissner, A.; Sharma, S.V.; Isselbacher, K.J.; Settleman, J.; Haber, D.A. Irreversible inhibitors of the EGFR receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci USA 2005, 102, 7665-7670.
19. Costa, D.B.; Kobayashi, S.; Tenen, D.G.; Huberman, M.S. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer 2007, 58, 95-103.
20. Greulich, H.; Chen, T.H.; Feng, W.; Jänne, P.A.; Alvarez, J.V.; Zappaterra, M.; Bulmer, S.E.; Frank, D.A.; Hahn, W.C.; Sellers, W.R.; Meyerson, M. Oncogenic transformation by inhibitorsensitive and -resistant EGFR mutants. PLoS Med 2005, 2, e313.
21. Maheswaran, S.; Sequist, L.V.; Nagrath, S.; Ulkus, L. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008, 359, 366-377.
22. Herbst, R.S.; Heymach, L.V.; Lippman, S.M. Lung cancer. N Engl J Med 2008, 359, 1367-1370.
23. Shih, J.Y.; Gow, C.H.; Yang, P.C. EGFRmutation conferring primary resistance to gefitinib in non-small cell lung cancer. N Engl J Med 2005, 353, 207-208.
24. Pao, W.; Wang, T.Y.; Riely, G.J.; Miller, V.A.; Pan, Q.; Ladanyi, M.; Zakowski, M.F.; Heelan, R.T.; Kris, M.G.; Varmus, H.E. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005, 2, e17.
25. Miller, V.A.; Zakowski, M.; Riely, G.J.; Pao, W.; Ladanyl, M.; Tsao, A.S.; Sandler, A.; Herbst, R.; Kris, M.G.; Johnson, D.H. EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): results of a perspective phase II trial (abstract no. 7003). J Clin Oncol 2006, 24, 364s.
26. Tsao, M.; Zhu, C.; Sakurada, A.; Zhang, T.;Whitehead, M.; Kamel-Reid, S.; Ding, K.; Seymour, L.; Shepherd, F. 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 (abstact no. 7005). J Clin Oncol 2006, 24, 365s.
27. Zhu, C.Q.; da Cunha, S.G.; Ding, K.; Sakurada, A.; Cutz, J.C.; Liu, N.; Zhang, T.; Marrano, P.; Whitehead, M.; Squire, J.A.; Kamel-Reid, S.; Seymour, L.; Shepherd, F.A.; Tsao, M.S. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008, 26, 4268-4275.
28. Brugger, W.; Kim, J.; Hansen, O.; Sullivan, R.N.; White, S.C.; Lee, J.; Klingelschmitt, G.; Spleiss, O.; Nagelmeier, I.; Cappuzzo, F. Molecular markers and clinical outcome with erlotinib: results from the phase III placebo-controlled SATURN study of maintenance therapy for advanced NSCLC. Paper presented at the 13th Annual World Conference on Lung Cancer, San Francisco, CA, July 31-August 4, 2009.
29. Bianco, R.; Shin, I.; Ritter, C.A.; Yakes, F.M.; Basso, A.; Rosen, N.; Tsurutani, J.; Dennis, P.A.; Mills, G.B.; Arteaga, C.L. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene 2003, 22, 2812-2822.
30. Tang, J.M.; He, Q.Y.; Guo, R.X.; Chang, X.J. Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer 2006, 51, 181-191.
31. Lim, W.T.; Zhang, W.H.; Miller, C.R.; Watters, J.W.; Gao, F.; Viswanathan, A.; Govindan, R.; McLeod, H.L. PTEN and phosphorylated AKT expression and prognosis in early-and late-stage non-small cell lung cancer. Oncol Rep 2007, 17, 853-857.
32. Cappuzzo, F.; Jänne, P.A.; Skokan, M.; Finocchiaro, G.; Rossi, E.; Ligorio, C.; Zucali, P.A.; Terracciano, L.; Toschi, L.; Roncalli, M.; Destro, A.; Incarbone, M.; Alloisio, M.; Santoro, A.; Varella-Garcia, M. MET increased gene copy number and primary resistance to gefitinib therapy in non-small cell lung cancer patients. Ann Oncol 2009, 20, 298-304.
33. Bean, J.; Brennan, C.; Shih, J.Y.; Riely, G.; Viale, A.; Wang, L.; Chitale, D.; Motoi, N.; Szoke, J.; Broderick, S.; Balak, M.; Chang, W.C.; Yu, C.J.; Gazdar, A.; Pass, H.; Rusch, V.; Gerald,W.; Huang, S.F.; Yang, P.C.; Miller, V.; Ladanyi, M.; Yang, C.H.; Pao, W. 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 2007, 104, 20932-20937.
34. Balak, M.N.; Gong, Y.; Riely, G.J.; Somwar, R.; Li, A.R.; Zakowski, M.F.; Chiang, A.; Yang, G.; Ouerfelli, O.; Kris, M.G.; Ladanyi, M.; Miller, V.A.; Pao, W. 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.
35. Kosaka, T.; Yatabe, Y.; Endoh, H.; Yoshida, K.; Hida, T.; Tsuboi, M.; Tada, H.; Kuwano, H.; Mitsudomi, T. Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res 2006, 12, 5764-5769.
36. Pao,W.;Miller, V.A.; Politi, K.A.; Riely, G.J.; Somwar, R.; Zakowski, M.F.; Kris, M.G.; Varmus, H. 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.
37. Kumar, A.; Petri, E.T.; Halmos, B.; Boggon, TJ. Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 2008, 26, 1742-1751.
38. Wood, E.R.; Truesdale, A.T.; McDonald, O.B.; Yuan, D.; Hassell, A.; Dickerson, S.H.; Ellis, B.; Pennisi, C.; Horne, E.; Lackey, K.; Alligood, K.J.; Rusnak, D.W.; Gilmer, T.M.; Shewchuk, L. A unique structure for epidermal growth factor receptor bound to GW572016 (lapatinib): relationships among protein conformation, inhibitor offrate, and receptor activity in tumor cells. Cancer Res 2004, 64, 6652-6659.
39. Jiang, S.X.; Yamashita, K.; Yamamoto, M.; Piao, C.J.; Umezawa, A.; Saegusa, M.; Yoshida, T.; Katagiri, M.; Masuda, N.; Hayakawa, K.; Okayasu, I. EGFR genetic heterogeneity of non-small cell lung cancers contributing to acquired gefitinib resistance. Int J Cancer 2008, 123, 2480-2486.
40. Engelman, J.A.; Zejnullahu, K.; Mitsudomi, T.; Song, Y.; Hyland, C.; Park, J.O.; Lindeman, N.; Gale, C.M.; Zhao, X.; Christensen, J.; Kosaka, T.; Holmes, A.J.; Rogers, A.M.; Cappuzzo, F.; Mok, T.; Lee, C.; Johnson, B.E.; Cantley, L.C.; Jänne, P.A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316, 1039-1043.
41. Morgillo, F.; Kim, W.Y.; Kim, E.S.; Ciardiello, F.; Hong, W.K.; Lee, H.Y. 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, 2795-2803.
42. Fidler, M.J.; Basu, S.; Buckingham, L.; et al. Insulin-like growth factor receptor 1 (IGFR-1) and outcome measures in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib (abstract no. 8036). J Clin Oncol 2008, 26, 432s.
43. Barr, S.; Thomson, S.; Buck, E.; Russo, S.; Petti, F.; Sujka-Kwok, I.; Eyzaguirre, A.; Rosenfeld-Franklin, M.; Gibson, N.W.; Miglarese, M.; Epstein, D.; Iwata, K.K.; Haley, J.D. Bypassing cellular EGF receptor dependence through epithelial-tomesenchymal-like transitions. Clin Exp Metastasis 2008, 25, 685-693.
44. Yauch, R.L.; Januario, T.; Eberhard, D.A.; Cavet, G.; Zhu, W.; Fu, L.; Pham, T.Q.; Soriano, R.; Stinson, J.; Seshagiri, S.; Modrusan, Z.; Lin, C.Y.; O'Neill, V.; Amler, L.C. Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin Cancer Res 2005, 11, 8686-8698.
45. Rho, J.K.; Choi, Y.J.; Lee, J.K.; Ryoo, B.Y.; Na, I.I.; Yang, S.H.; Kim, C.H.; Lee, J.C. Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer 2009, 63, 219-226.
46. Elkind, N.B.; Szentpetery, Z.; Apati, A.;Ozvegy-Laczka, C.; Varady, G.; Ujhelly, O.; Szabo, K.; Homolya, L.; Varadi, A.; Buday, L.; Keri, G.; Nemet, K.; Sarkadi, B. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib). Cancer Res 2005, 65, 1770-1777.
47. Benavente, S.; Huang, S.; Armstrong, E.; Chi, A.; Hsu, K.;Wheeler, D.; Harari, P. Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells. Clin Cancer Res 2009, 15, 1585-1592.
48. Wissner, A.; Mansour, T.S. The development of HKI-272 and related compounds for the treatment of cancer. Arch Pharm (Weinheim) 2008, 341, 465-477.
49. Yun, C.H.; Mengwasser, K.E.; Toms, A.V.; Woo, M.S.; Greulich, H.; Wong, K.K.; Meyerson, M.; Eck, M.J. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008, 105, 2070-2075.
50. Kobayashi, S.; Boggon, T.J.; Dayaram, T.; Jänne, P.A.; Kocher, O.; Meyerson, M.; Johnson, B.E.; Eck, M.J.; Tenen, D.G.; Halmos, B. EGFR mutation and resistance of non-small cell lung cancer to gefitinib. N Engl J Med 2005, 352, 786-792. (Pubitemid 40271173)
51. Li, D.; Ambrogio, L.; Shimamura, T.; Kubo, S.; Takahashi, M.; Chirieac, L.R.; Padera, R.F.; Shapiro, G.I.; Baum, A.; Himmelsbach, F.; Rettig, W.J.; Meyerson, M.; Solca, F.; Greulich, H.; Wong, K.K. BIBW 2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008, 27, 4702-4711.
52. Engelman, J.A.; Zejnullahu, K.; Gale, C.M.; Lifshits, E.; Gonzales, A.J.; Shimamura, T.; Zhao, F.; Vincent, P.W.; Naumov, G.N.; Bradner, J.E.; Althaus, I.W.; Gandhi, L.; Shapiro,G.I.; Nelson, J.M.; Heymach, J.V.; Meyerson, M.; Wong, K.K.; Jänne, P.A. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res 2007, 67, 11924-11932.
53. Jänne, P.A.; von Pawel, J.; Cohen, R.B.; Crino, L.; Butts, C.A.; Olson, S.S.; Eiseman, I.A.; Chiappori, A.A.; Yeap, B.Y.; Lenehan, P.F.; Dasse, K.; Sheeran, M.; Bonomi, P.D. Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non small-cell lung cancer. J Clin Oncol 2007, 25, 3936-3944.
54. Normanno, N.; Bianco, C.; Strizzi, L.; Mancino, M.; Maiello, M.R.; De Luca, A.; Caponigro, F.; Salomon, D.S. The ErbB receptors and their ligands in cancer: an overview. Curr Drug Targets 2005, 6, 243-257.
55. Pinkas-Kramarski, R.; Soussan, L.; Waterman, H.; Levkowitz, G.; Alroy, I.; Klapper, L.; Lavi, S.; Seger, R.; Ratzkin, B.J.; Sela, M.; Yarden, Y. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 1996, 15, 2452-2467. (Pubitemid 26151185)
56. Worthylake, R.; Opresko, L.K.; Wiley, H.S. ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 1999, 274, 8865-8874. (Pubitemid 29164687)
57. Brabender, J.; Danenberg, K.D.; Metzger, R.; Schneider, P.M.; Park, J.; Salonga, D.; Holscher, A.H.; Danenberg, P.V. Epidermal growth factor receptor and HER2-neu mRNA expression in nonsmall cell lung cancer is correlated with survival. Clin Cancer Res 2001, 7, 1850-1855. (Pubitemid 32994816)
58. Onn, A.; Correa, A.M.; Gilcrease, M.; Isobe, T.; Massarelli, E.; Bucana, C.D.; O'Reilly, M.S.; Hong, W.K.; Fidler, I.J.; Putnam, J.B.; Herbst, R.S. Synchronous overexpression of epidermal growth factor receptor and HER2-neu protein is a predictor of poor outcome in patients with stage I non-small cell lung cancer. Clin Cancer Res 2004, 10, 136-143. (Pubitemid 38114172)
59. Tateishi, M.; Ishida, T.; Kohdono, S.; Hamatake, M.; Fukuyama, Y.; Sugimachi, K. Prognostic influence of the coexpression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma. Surg Oncol 1994, 3, 109-113. (Pubitemid 24237138)
60. Smylie, M.; Blumenschein, G.; Dowlati, A. A phase II multicenter trial comparing two schedules of lapatinib (LAP) as first or second line monotherapy in subjects with advanced or metastatic non-small cell lung cancer (NSCLC) with either bronchioloalveolar carcinoma (BAC) or no smoking history (abstract no. 7611). J Clin Oncol 2007, 25, 412s.
61. Kobayashi, S.; Ji, H.; Yuza, Y.; Meyerson, M.; Wong, K.K.; Tenen, D.G.; Halmos, B. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res 2005, 65, 7096-7101. (Pubitemid 41161238)
62. Suzuki, T.; Fujii, A.; Ohya, J.; Amano, Y.; Kitano, Y.; Abe, D.; Nakamura, H. Pharmacological characterization of MP-412 (AV-412), a dual epidermal growth factor receptor and ErbB2 tyrosine kinase inhibitor. Cancer Sci 2007, 98, 1977-1984. (Pubitemid 350002206)
63. Shimamura, T.; Ji, H.; Minami, Y.; Thomas, R.K.; Lowell, A.M.; Shah, K.; Greulich, H.; Glatt, K.A.; Meyerson, M.; Shapiro, G.I.; Wong, K.K. Non-small cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. Cancer Res 2006, 66, 6487-6491. (Pubitemid 44085601)
64. Eskens, F.A.; Mom, C.H.; Planting, A.S.;Gietema, J.A.; Amelsberg, A.; Huisman, H.; van Doorn, L.; Burger, H.; Stopfer, P.; Verweij, J.; de Vries, E.G. A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 2008, 98, 80-85.
65. Agus, D.; Terlizzi, E.; Stopfer, P.; Amelsberg, A.; Gordon, M. A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a continuous schedule in patients with advanced solid tumors. Paper presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.
66. Lewis, N.; Marshall, J.; Amelsberg, A.; Cohen, R.; Stopfer, P.; Hwang, J.; Malik, S. A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a 3-week on 1-week off schedule in patients with advanced solid tumors (abstract no. 3091). J Clin Oncol 2006, 24, 143s.
67. Shaw, H.; Plummer, R.; Vidal, L.; Perrett, R.; Pilkington, G.; Temple, G.; Fong, P.; Amelsberg, A.; Calvert, H.; De Bono. J. A phase I dose escalation study of BIBW 2992, an irreversible duel EGFR/FER2 receptor tyrosine kinase inhibitor, in patients with advanced solid tumours (abstract no. 3027). J Clin Oncol 2006, 24, 127s.
68. Stopfer, P.; Schaefer, H.; Amelsberg, A.; Huisman, H.; Eskens, F.; Gietema, J.; Briscoe, J.; Lewis, N.; Cohen, R.;Marshall, J.; Verweij, J. Pharmacokinetic results from two phase I dose escalation studies of once daily oral treatment with BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in patients with advanced solid tumors (abstract no. B172). Clin Cancer Res 2005, 11, 9075s.
69. Plummer, R.; Vidal, L.; Li, L.; Shaw, H.; Perrett, R.; Shahidi, M.; Amelsberg, A.; Temple, G.; Calvert, H.; de Bono, J. Phase I study of BIBW 2992, an oral irreversible dual EGFR/HER2 inhibitor, showing activity in tumors with mutated EGFR (abstract no. 573). Eur J Cancer 2006, 4, 173-174.
70. Shih, J.; Yang, C.; Su,W.C.; Hsia, T.; Tsai, C.; Chen, Y.; Chang, H.; Terlizzi, E.; Shahidi, V.A. A phase II study of BIBW 2992, a novel irreversible dual EGFR and HER2 tyrosine kinase inhibitor (TKI), in patients with adenocarcinoma of the lung and activating EGFR mutations after failure of one line of chemotherapy (LUX-Lung 2) (abstract no. 8013), J Clin Oncol 2009, 27, 15s.
71. Yang, C.H.; Shih, J.Y.; Su, W.C.; Hsia, H.-C.; Ho, C.-L.; Dudek, A.Z.; Terlizzi, E.; Zhao, Y.M.; Shahidi, M.; Miller, V.A. BIBW 2992, a reversible EGFR/HER2 tyrosine kinase inhibitor, in chemonaive patients with adenocarcinoma of the lung and activating EGFR mutations. Paper presented at the 13thWorld Conference on Lung Cancer, San Francisco, CA, July 31-August 4, 2009.
72. ClinicalTrials.gov. Single-arm trial of BIBW 2992 (TOVOK) in demographically and genotypically selected NSCLC patients. Retrieved November 2, 2009, from http://clinicaltrials.gov/ct2/show/NCT00730925?term= NCT00730925&rank=1.
73. ClinicalTrials.gov. LUX Lung 2 a phase II single-arm study of BIBW 2992 in NSCLC patients who have failed one line of chemotherapy or are chemotherapy naive and who have EGFR activating mutations. Retrieved November 2, 2009, from http://clinicaltrials.gov/ct2/show/NCT00525148?term=NCT00525148&rank=1.
74. ClinicalTrials.gov. Phase I/II open label trial of continuous once daily oral treatment with BIBW 2992-phase I trial in advanced non-small cell lung cancer patients & phase II trial in non-small cell lung cancer patients failing erlotinib or gefitinib. Retrieved October 29, 2009, from http://www.clinicaltrials.gov/ct2/show/NCT00711594?term=BIBW&cond= NSCLC&rank=1. Last updated October 12, 2009.
75. ClinicalTrials.gov. BIBW 2992 and BSC versus placebo and BSC in non-small sell lung cancer patients failing erlotinib or gefitinib (LUX-LUNG 1). Retrieved October 29, 2009, from http://www.clinicaltrials.gov/ct2/show/ NCT00656136?term=bibw 2992&rank=11. Last updated October 12, 2009.
76. Yang, C.; Hirsh, V.; Cadranel, J.; Chen, Y.; Park, K.; Kim, S.; Chao, T.; Oberdick, M.; Shahidi, M.; Miller, V. Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible, dual inhibitor of EGFR and HER2 plus best supportive care (BSC) versus placebo plus BSC in patients with NSCLC failing 1-2 lines of chemotherapy (CT) and erlotinib or gefitinib (LUX-Lung 1): a preliminary report (abstract no. 8062), J Clin Oncol 2009, 27, 15s.
77. Wong, K.K.; Fracasso, P.M.; Bukowski, R.M.; Lynch, T.J.; Munster, P.N.; Shapiro, G.I.; Jänne, P.A.; Eder, J.P.; Naughton, M.J.; Ellis, M.J.; Jones, S.F.; Mekhail, T.; Zacharchuk, C.; Vermette, J.; Abbas, R.; Quinn, S.; Powell, C.; Burris, H.A. A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res 2009, 15, 2552-2558.
78. Yoshimura, N.; Kudoh, S.; Kimura, T.; Mitsuoka, S.; Matsuura, K.; Hirata, K.; Matsui, K.; Negoro, S.; Nakagawa, K.; Fukuoka, M. EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with non-small cell lung cancer with acquired resistance to gefitinib. Lung Cancer 2006, 51, 363-368. (Pubitemid 43265820)
79. Nemunaitis, J.; Eiseman, I.; Cunningham, C.; Senzer, N.; Williams, A.; Lenehan, P.F.; Olson, S.C.; Bycott, P.; Schlicht, M.; Zentgraff, R.; Shin, D.M.; Zinner, R.G. Phase 1 clinical and pharmacokinetics evaluation of oral CI-1033 in patients with refractory cancer. Clin Cancer Res 2005, 11, 3846-3853. (Pubitemid 40685605)
80. Jänne, P.A.; Schellens, J.H.; Engelman, J.A.; Eckhardt, S.G.; Millham, R.; Denis, L.J.; Britten, C.D.; Wong, S.G., Boss, D.S.; Camidge, D.R. Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC (abstract no. 8027). J Clin Oncol 2008, 26, 430s.
81. Jänne, P.A.; Reckamp, K.L.; Koczywas, M.; Engelman, J.A.; Camidge, D.R.; Rajan, A.; Khuri, F.; Liang, J.Q.; O'Connell, J.; Giaccone, G. Efficacy and safety of PF-00299804 (PF299) in patients (pt) with advanced NSCLC after failure of at least one prior chemotherapy regimen and prior treatment with erlotinib (E): a two-arm, phase II trial (abstract no. 8063). J Clin Oncol 2009, 27.
82. ClinicalTrials.gov. A randomized trial of PF-00299804 taken orally versus erlotinib taken orally for treatment of advanced non-small cell lung cancer that has progressed after one or two prior chemotherapy regimen [sic]. Retrieved October 29, 2009, from http://clinicaltrials.gov/ct2/show/NCT00769067?term= PF00299804 & rank=4. Last updated October 16, 2009.
83. ClinicalTrials.gov. A safety study of an oral EGFR inhibitor, AV-412, administered three times weekly in advanced solid tumor patients. Retrieved October 29, 2009, from http://clinicaltrials.gov/ct2/show/NCT00551850?term=MP- 412&rank=1. Last updated January 23, 2009.
84. ClinicalTrials.gov. Safety/tolerability study of AV-412 in subjects with refractory or relapsed solid tumormalignancies. Retrieved October 29, 2009, from http://clinicaltrials.gov/ct2/show?term=MP-412&rank2. Last updated July 29, 2009.