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Published in: Targeted Oncology 4/2010

01-12-2010 | Review

EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992

Authors: James F. Spicer, Sarah M. Rudman

Published in: Targeted Oncology | Issue 4/2010

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Abstract

Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer and is associated with significant mortality and morbidity worldwide. Despite improvements in conventional treatment for NSCLC, survival remains poor and improvements in patient outcome are warranted. Over recent years, basic scientific research has dramatically increased our knowledge of the pathogenesis of lung cancer and allowed us to uncover and understand the cellular pathways involved in this process. This has led to the development of therapies to selectively target these pathways. Among these, the epidermal growth factor receptor (EGFR) tyrosine kinase family and related downstream pathways play a critical role in cancer development and over recent years have become a validated target in NSCLC. The development of monoclonal antibodies and first-generation tyrosine kinase inhibitors (TKIs) targeted towards EGFR has had a considerable impact on patient outcomes. However, despite dramatic and sustained responses and the discovery of specific patient subgroups that may derive clinical benefit, resistance to first-generation EGFR TKIs inevitably develops. A new generation of agents have been developed to provide superior potency of target inhibition and further individualize the treatment of NSCLC. This article reviews EGFR-targeted therapies currently available for use and undergoing clinical development for the treatment of NSCLC, specifically focusing on next generation agents including BIBW 2992, an irreversible dual inhibitor of EGFR and HER2 kinases.
Literature
1.
go back to reference Kung HC, Hoyert DL, Xu J, Murphy SL (2008) Deaths: final data for 2005. Natl Vital Stat Rep 56(10):1–120PubMed Kung HC, Hoyert DL, Xu J, Murphy SL (2008) Deaths: final data for 2005. Natl Vital Stat Rep 56(10):1–120PubMed
2.
go back to reference U.S. Cancer Statistics Working Group (2007) United States Cancer Statistics: 2004 Incidence and Mortality. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute: Atlanta U.S. Cancer Statistics Working Group (2007) United States Cancer Statistics: 2004 Incidence and Mortality. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute: Atlanta
3.
go back to reference American Cancer Society (2009) Cancer Facts and Figures 2009, 15 American Cancer Society (2009) Cancer Facts and Figures 2009, 15
4.
go back to reference Sculier J-P, Moro-Sibilot D (2009) First- and second-line therapy for advanced nonsmall cell lung cancer. Eur Respir J 33(4):915–930 Sculier J-P, Moro-Sibilot D (2009) First- and second-line therapy for advanced nonsmall cell lung cancer. Eur Respir J 33(4):915–930
5.
go back to reference Bedano PM, Hanna NH (2006) Salvage therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 1(6):582–587CrossRefPubMed Bedano PM, Hanna NH (2006) Salvage therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 1(6):582–587CrossRefPubMed
6.
go back to reference Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19(56):6550–6565CrossRefPubMed Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19(56):6550–6565CrossRefPubMed
7.
go back to reference Pinkas-Kramarski R, Soussan L, Waterman H, Levkowitz G, Alroy I, Klapper L, Lavi S, Seger R, Ratzkin BJ, Sela M, Yarden Y (1996) Diversification of Neu differentiation factor and epidermal growth factor signalling by combinatorial receptor interactions. EMBO J 15(10):2452–2467PubMed Pinkas-Kramarski R, Soussan L, Waterman H, Levkowitz G, Alroy I, Klapper L, Lavi S, Seger R, Ratzkin BJ, Sela M, Yarden Y (1996) Diversification of Neu differentiation factor and epidermal growth factor signalling by combinatorial receptor interactions. EMBO J 15(10):2452–2467PubMed
8.
go back to reference Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, Ratzkin BJ, Yarden Y (1996) A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 16(10):5276–5287PubMed Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, Ratzkin BJ, Yarden Y (1996) A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 16(10):5276–5287PubMed
9.
go back to reference Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, Yarden Y (1999) The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A 96(9):4995–5000CrossRefPubMed Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, Yarden Y (1999) The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A 96(9):4995–5000CrossRefPubMed
10.
go back to reference Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358(11):1160–1174CrossRefPubMed Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358(11):1160–1174CrossRefPubMed
11.
go back to reference Dassonville O, Bozec A, Fischel JL, Milano G (2007) EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences. Crit Rev Oncol Hematol 62(1):53–61CrossRefPubMed Dassonville O, Bozec A, Fischel JL, Milano G (2007) EGFR targeting therapies: monoclonal antibodies versus tyrosine kinase inhibitors. Similarities and differences. Crit Rev Oncol Hematol 62(1):53–61CrossRefPubMed
12.
go back to reference Salomon DS, Brandt R, Ciardiello F, Normanno N (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19(3):183–232CrossRefPubMed Salomon DS, Brandt R, Ciardiello F, Normanno N (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19(3):183–232CrossRefPubMed
13.
go back to reference Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7(7):505–516CrossRefPubMed Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7(7):505–516CrossRefPubMed
14.
go back to reference Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354CrossRefPubMed Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354CrossRefPubMed
15.
go back to reference Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353(2):172–187CrossRefPubMed Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353(2):172–187CrossRefPubMed
16.
17.
go back to reference Imai K, Takaoka A (2006) Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 6(9):714–727CrossRefPubMed Imai K, Takaoka A (2006) Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 6(9):714–727CrossRefPubMed
18.
go back to reference Rossi A, Maione P, Gridelli C (2006) Cetuximab in advanced non-small cell lung cancer. Crit Rev Oncol Hematol 59(2):139–149CrossRefPubMed Rossi A, Maione P, Gridelli C (2006) Cetuximab in advanced non-small cell lung cancer. Crit Rev Oncol Hematol 59(2):139–149CrossRefPubMed
19.
go back to reference Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O’Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373(9674):1525–1531CrossRefPubMed Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O’Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373(9674):1525–1531CrossRefPubMed
20.
go back to reference Baselga J (2002) Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 7(Suppl 4):2–8CrossRefPubMed Baselga J (2002) Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 7(Suppl 4):2–8CrossRefPubMed
21.
go back to reference Blackhall F, Ranson M, Thatcher N (2006) Where next for gefitinib in patients with lung cancer? Lancet Oncol 7(6):499–507CrossRefPubMed Blackhall F, Ranson M, Thatcher N (2006) Where next for gefitinib in patients with lung cancer? Lancet Oncol 7(6):499–507CrossRefPubMed
22.
go back to reference Baselga J, Rischin D, Ranson M, Calvert H, Raymond E, Kieback DG, Kaye SB, Gianni L, Harris A, Bjork T, Averbuch SD, Feyereislova A, Swaisland H, Rojo F, Albanell J (2002) Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 20(21):4292–4302CrossRefPubMed Baselga J, Rischin D, Ranson M, Calvert H, Raymond E, Kieback DG, Kaye SB, Gianni L, Harris A, Bjork T, Averbuch SD, Feyereislova A, Swaisland H, Rojo F, Albanell J (2002) Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 20(21):4292–4302CrossRefPubMed
23.
go back to reference Hidalgo M, Siu LL, Nemunaitis J, Rizzo J, Hammond LA, Takimoto C, Eckhardt SG, Tolcher A, Britten CD, Denis L, Ferrante K, Von Hoff DD, Silberman S, Rowinsky EK (2001) 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 19(13):3267–3279PubMed Hidalgo M, Siu LL, Nemunaitis J, Rizzo J, Hammond LA, Takimoto C, Eckhardt SG, Tolcher A, Britten CD, Denis L, Ferrante K, Von Hoff DD, Silberman S, Rowinsky EK (2001) 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 19(13):3267–3279PubMed
24.
go back to reference Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, 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 RP, Baselga J (2003) 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 21(12):2237–2246CrossRefPubMed Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, 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 RP, Baselga J (2003) 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 21(12):2237–2246CrossRefPubMed
25.
go back to reference Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC (2003) 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 290(16):2149–2158CrossRefPubMed Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC (2003) 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 290(16):2149–2158CrossRefPubMed
26.
go back to reference Perez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, Rigas J, Clark GM, Santabarbara P, Bonomi P (2004) Determinants of tumor response and survival with erlotinib in patients with non–small-cell lung cancer. J Clin Oncol 22(16):3238–3247CrossRefPubMed Perez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, Rigas J, Clark GM, Santabarbara P, Bonomi P (2004) Determinants of tumor response and survival with erlotinib in patients with non–small-cell lung cancer. J Clin Oncol 22(16):3238–3247CrossRefPubMed
27.
go back to reference Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, 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 (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132CrossRefPubMed Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, 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 (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132CrossRefPubMed
28.
go back to reference Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K (2005) 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):1527–1537CrossRefPubMed Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K (2005) 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):1527–1537CrossRefPubMed
29.
go back to reference Clark G (2008) Prognostic factors versus predictive factors: examples from a clinical trial of erlotinib. Mol Oncol 1(4):406–412CrossRefPubMed Clark G (2008) Prognostic factors versus predictive factors: examples from a clinical trial of erlotinib. Mol Oncol 1(4):406–412CrossRefPubMed
30.
go back to reference Miller VA, Kris MG, Shah N, Patel J, Azzoli C, Gomez J, Krug LM, Pao W, Rizvi N, Pizzo B, Tyson L, Venkatraman E, Ben-Porat L, Memoli N, Zakowski M, Rusch V, Heelan RT (2004) Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol 22(6):1103–1109CrossRefPubMed Miller VA, Kris MG, Shah N, Patel J, Azzoli C, Gomez J, Krug LM, Pao W, Rizvi N, Pizzo B, Tyson L, Venkatraman E, Ben-Porat L, Memoli N, Zakowski M, Rusch V, Heelan RT (2004) Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol 22(6):1103–1109CrossRefPubMed
31.
go back to reference Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957CrossRefPubMed Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957CrossRefPubMed
32.
go back to reference Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139CrossRefPubMed Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139CrossRefPubMed
33.
go back to reference Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500CrossRefPubMed Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500CrossRefPubMed
34.
go back to reference Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H (2004) 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 101(36):13306–13311CrossRefPubMed Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H (2004) 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 101(36):13306–13311CrossRefPubMed
35.
go back to reference Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181CrossRefPubMed Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181CrossRefPubMed
36.
go back to reference Riely GJ, Politi KA, Miller VA, Pao W (2006) Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res 12(24):7232–7241CrossRefPubMed Riely GJ, Politi KA, Miller VA, Pao W (2006) Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res 12(24):7232–7241CrossRefPubMed
37.
go back to reference Sequist LV, Lynch TJ (2008) EGFR tyrosine kinase inhibitors in lung cancer: an evolving story. Annu Rev Med 59:429–442CrossRefPubMed Sequist LV, Lynch TJ (2008) EGFR tyrosine kinase inhibitors in lung cancer: an evolving story. Annu Rev Med 59:429–442CrossRefPubMed
38.
go back to reference Riely GJ, Pao W, Pham D, Li AR, Rizvi N, Venkatraman ES, Zakowski MF, Kris MG, Ladanyi M, Miller VA (2006) 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 12(3 Pt 1):839–844CrossRefPubMed Riely GJ, Pao W, Pham D, Li AR, Rizvi N, Venkatraman ES, Zakowski MF, Kris MG, Ladanyi M, Miller VA (2006) 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 12(3 Pt 1):839–844CrossRefPubMed
39.
go back to reference Sequist LV, Bell DW, Lynch TJ, Haber DA (2007) Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 25(5):587–595CrossRefPubMed Sequist LV, Bell DW, Lynch TJ, Haber DA (2007) Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 25(5):587–595CrossRefPubMed
40.
go back to reference Jackman DM, Yeap BY, Sequist LV, Lindeman N, Holmes AJ, Joshi VA, Bell DW, Huberman MS, Halmos B, Rabin MS, Haber DA, Lynch TJ, Meyerson M, Johnson BE, Janne PA (2006) 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 12(13):3908–3914CrossRefPubMed Jackman DM, Yeap BY, Sequist LV, Lindeman N, Holmes AJ, Joshi VA, Bell DW, Huberman MS, Halmos B, Rabin MS, Haber DA, Lynch TJ, Meyerson M, Johnson BE, Janne PA (2006) 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 12(13):3908–3914CrossRefPubMed
41.
go back to reference Yang C, Shih J, Su W, Hsia T, Ho C, Dudek AZ, Terlizzi E, Zhao Y, Shahidi M, Miller VA (2009) BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor, in chemonaïve patients with adenocarcinoma of the lung and activating EGFR mutations. J Thor Oncol 4 (suppl 1):Abstract A3.3 Yang C, Shih J, Su W, Hsia T, Ho C, Dudek AZ, Terlizzi E, Zhao Y, Shahidi M, Miller VA (2009) BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor, in chemonaïve patients with adenocarcinoma of the lung and activating EGFR mutations. J Thor Oncol 4 (suppl 1):Abstract A3.3
42.
go back to reference Sasaki H, Endo K, Takada M, Kawahara M, Kitahara N, Tanaka H, Okumura M, Matsumura A, Iuchi K, Kawaguchi T, Kawano O, Yukiue H, Yokoyama T, Yano M, Fujii Y (2007) EGFR exon 20 insertion mutation in Japanese lung cancer. Lung Cancer 58(3):324–328CrossRefPubMed Sasaki H, Endo K, Takada M, Kawahara M, Kitahara N, Tanaka H, Okumura M, Matsumura A, Iuchi K, Kawaguchi T, Kawano O, Yukiue H, Yokoyama T, Yano M, Fujii Y (2007) EGFR exon 20 insertion mutation in Japanese lung cancer. Lung Cancer 58(3):324–328CrossRefPubMed
43.
go back to reference Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sanchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967CrossRefPubMed Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sanchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967CrossRefPubMed
44.
go back to reference Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT, Kris MG, Sandler AB, Carbone DP, Tsao A, Herbst RS, Heller G, Ladanyi M, Pao W, Johnson DH (2008) Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol 26(9):1472–1478CrossRefPubMed Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT, Kris MG, Sandler AB, Carbone DP, Tsao A, Herbst RS, Heller G, Ladanyi M, Pao W, Johnson DH (2008) Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol 26(9):1472–1478CrossRefPubMed
45.
go back to reference Sequist LV, Martins R, Spigel D, Grunberg SM, Janne PA, McCollum D, Spira A, Evans T, Johnson BE, Lynch TJ (2007) iTARGET: a phase II trial to assess the response to gefitinib in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) tumors. J Clin Oncol 25(18S):Abstract 7504 Sequist LV, Martins R, Spigel D, Grunberg SM, Janne PA, McCollum D, Spira A, Evans T, Johnson BE, Lynch TJ (2007) iTARGET: a phase II trial to assess the response to gefitinib in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) tumors. J Clin Oncol 25(18S):Abstract 7504
46.
go back to reference ClinicalTrials.gov (2008) Phase III study (Tarceva®) vs chemotherapy to treat advanced non-small cell lung cancer (NSCLC) in patients with mutations in the TK domain of EGFR. Available from: www.clinicaltrials.gov. Cited February 1, 2010 ClinicalTrials.gov (2008) Phase III study (Tarceva®) vs chemotherapy to treat advanced non-small cell lung cancer (NSCLC) in patients with mutations in the TK domain of EGFR. Available from: www.​clinicaltrials.​gov. Cited February 1, 2010
47.
go back to reference Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Doglioni C, Sidoni A, Tonato M, Franklin WA, Crino L, Bunn PA Jr, Varella-Garcia M (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97(9):643–655CrossRefPubMed Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Doglioni C, Sidoni A, Tonato M, Franklin WA, Crino L, Bunn PA Jr, Varella-Garcia M (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97(9):643–655CrossRefPubMed
48.
go back to reference Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerlock P, Bunn PA Jr, Franklin WA, Crowley J, Gandara DR (2005) 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 23(28):6838–6845CrossRefPubMed Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerlock P, Bunn PA Jr, Franklin WA, Crowley J, Gandara DR (2005) 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 23(28):6838–6845CrossRefPubMed
49.
go back to reference Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha SG, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA (2005) Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med 353(2):133–144CrossRefPubMed Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha SG, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA (2005) Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med 353(2):133–144CrossRefPubMed
50.
go back to reference Toschi L, Cappuzzo F (2007) Understanding the new genetics of responsiveness to epidermal growth factor receptor tyrosine kinase inhibitors. Oncologist 12(2):211–220CrossRefPubMed Toschi L, Cappuzzo F (2007) Understanding the new genetics of responsiveness to epidermal growth factor receptor tyrosine kinase inhibitors. Oncologist 12(2):211–220CrossRefPubMed
51.
go back to reference Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792CrossRefPubMed Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792CrossRefPubMed
52.
go back to reference Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73CrossRefPubMed Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73CrossRefPubMed
53.
go back to reference Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377CrossRefPubMed Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377CrossRefPubMed
54.
go back to reference Bean J, Riely GJ, Balak M, Marks JL, Ladanyi M, Miller VA, Pao W (2008) 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 14(22):7519–7525CrossRefPubMed Bean J, Riely GJ, Balak M, Marks JL, Ladanyi M, Miller VA, Pao W (2008) 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 14(22):7519–7525CrossRefPubMed
55.
go back to reference Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, Chiang A, Yang G, Ouerfelli O, Kris MG, Ladanyi M, Miller VA, Pao W (2006) Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 12(21):6494–6501CrossRefPubMed Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, Chiang A, Yang G, Ouerfelli O, Kris MG, Ladanyi M, Miller VA, Pao W (2006) Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 12(21):6494–6501CrossRefPubMed
56.
go back to reference Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A 104(52):20932–20937CrossRefPubMed Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A 104(52):20932–20937CrossRefPubMed
57.
go back to reference Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Janne PA (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signalling. Science 316(5827):1039–1043CrossRefPubMed Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Janne PA (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signalling. Science 316(5827):1039–1043CrossRefPubMed
58.
go back to reference Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II (2007) KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 13(10):2890–2896CrossRefPubMed Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II (2007) KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 13(10):2890–2896CrossRefPubMed
59.
go back to reference Zhu CQ, da Cunha Santos G, Ding K, Sakurada A, Cutz JC, Liu N, Zhang T, Marrano P, Whitehead M, Squire JA, Kamel-Reid S, Seymour L, Shepherd FA, Tsao MS (2008) 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 26(26):4268–4275CrossRefPubMed Zhu CQ, da Cunha Santos G, Ding K, Sakurada A, Cutz JC, Liu N, Zhang T, Marrano P, Whitehead M, Squire JA, Kamel-Reid S, Seymour L, Shepherd FA, Tsao MS (2008) 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 26(26):4268–4275CrossRefPubMed
60.
go back to reference Kokai Y, Myers JN, Wada T, Brown VI, LeVea CM, Davis JG, Dobashi K, Greene MI (1989) Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts. Cell 58(2):287–292CrossRefPubMed Kokai Y, Myers JN, Wada T, Brown VI, LeVea CM, Davis JG, Dobashi K, Greene MI (1989) Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts. Cell 58(2):287–292CrossRefPubMed
61.
go back to reference Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, Di Fiore PP, Kraus MH (1995) Cooperative signalling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 10(9):1813–1821PubMed Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, Di Fiore PP, Kraus MH (1995) Cooperative signalling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 10(9):1813–1821PubMed
62.
go back to reference Motoyama AB, Hynes NE, Lane HA (2002) The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res 62(11):3151–3158PubMed Motoyama AB, Hynes NE, Lane HA (2002) The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res 62(11):3151–3158PubMed
63.
go back to reference Reid A, Vidal L, Shaw H, de Bono J (2007) Dual inhibition of ErbB1 (EGFR/HER1) + ErbB2 (HER2/neu). Eur J Cancer 43(3):481–489CrossRefPubMed Reid A, Vidal L, Shaw H, de Bono J (2007) Dual inhibition of ErbB1 (EGFR/HER1) + ErbB2 (HER2/neu). Eur J Cancer 43(3):481–489CrossRefPubMed
64.
go back to reference Xia W, Lau YK, Zhang HZ, Xiao FY, Johnston DA, Liu AR, Li L, Katz RL, Hung MC (1999) Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res 5(12):4164–4174PubMed Xia W, Lau YK, Zhang HZ, Xiao FY, Johnston DA, Liu AR, Li L, Katz RL, Hung MC (1999) Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res 5(12):4164–4174PubMed
65.
go back to reference Tateishi M, Ishida T, Kohdono S, Hamatake M, Fukuyama Y, Sugimachi K (1994) Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma. Surg Oncol 3(2):109–113CrossRefPubMed Tateishi M, Ishida T, Kohdono S, Hamatake M, Fukuyama Y, Sugimachi K (1994) Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma. Surg Oncol 3(2):109–113CrossRefPubMed
66.
go back to reference Nelson MH, Dolder CR (2007) A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer. Ther Clin Risk Manag 3(4):665–673PubMed Nelson MH, Dolder CR (2007) A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer. Ther Clin Risk Manag 3(4):665–673PubMed
67.
go back to reference Petrelli F, Cabiddu M, Cazzaniga ME, Cremonesi M, Barni S (2008) Targeted therapies for the treatment of breast cancer in the post-trastuzumab era. Oncologist 13(4):373–381CrossRefPubMed Petrelli F, Cabiddu M, Cazzaniga ME, Cremonesi M, Barni S (2008) Targeted therapies for the treatment of breast cancer in the post-trastuzumab era. Oncologist 13(4):373–381CrossRefPubMed
68.
go back to reference Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743CrossRefPubMed Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743CrossRefPubMed
69.
go back to reference Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE (2008) A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 112(3):533–543CrossRefPubMed Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE (2008) A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 112(3):533–543CrossRefPubMed
70.
go back to reference Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, Wistuba II, Fong KM, Toyooka S, Shimizu N, Fujisawa T, Minna JD, Gazdar AF (2005) Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 65(5):1642–1646CrossRefPubMed Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, Wistuba II, Fong KM, Toyooka S, Shimizu N, Fujisawa T, Minna JD, Gazdar AF (2005) Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 65(5):1642–1646CrossRefPubMed
71.
go back to reference Buttitta F, Barassi F, Fresu G, Felicioni L, Chella A, Paolizzi D, Lattanzio G, Salvatore S, Camplese PP, Rosini S, Iarussi T, Mucilli F, Sacco R, Mezzetti A, Marchetti A (2006) Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer 119(11):2586–2591CrossRefPubMed Buttitta F, Barassi F, Fresu G, Felicioni L, Chella A, Paolizzi D, Lattanzio G, Salvatore S, Camplese PP, Rosini S, Iarussi T, Mucilli F, Sacco R, Mezzetti A, Marchetti A (2006) Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer 119(11):2586–2591CrossRefPubMed
72.
go back to reference Kwak EL, Sordella R, Bell DW, Godin-Heymann N, Okimoto RA, Brannigan BW, Harris PL, Driscoll DR, Fidias P, Lynch TJ, Rabindran SK, McGinnis JP, Wissner A, Sharma SV, Isselbacher KJ, Settleman J, Haber DA (2005) Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci U S A 102(21):7665–7670CrossRefPubMed Kwak EL, Sordella R, Bell DW, Godin-Heymann N, Okimoto RA, Brannigan BW, Harris PL, Driscoll DR, Fidias P, Lynch TJ, Rabindran SK, McGinnis JP, Wissner A, Sharma SV, Isselbacher KJ, Settleman J, Haber DA (2005) Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci U S A 102(21):7665–7670CrossRefPubMed
73.
go back to reference Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H, Wong KK (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27(34):4702–4711CrossRefPubMed Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H, Wong KK (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27(34):4702–4711CrossRefPubMed
74.
go back to reference Solca F (2007) Pharmacology and molecular mechanisms of BIBW2992, a potent irreversible dual EGFR/HER2 kinase inhibitor for cancer therapy. Targ Oncol 2(1S):15 Solca F (2007) Pharmacology and molecular mechanisms of BIBW2992, a potent irreversible dual EGFR/HER2 kinase inhibitor for cancer therapy. Targ Oncol 2(1S):15
75.
go back to reference Solca F, Baum A, Guth B, Colbatzky F, Blech S, Amelsberg A, Himmelsbach F (2005) BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor for cancer therapy. Proceedings, AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Philadelphia, PA. 14–18 November 2005:118 (Abstract A244) Solca F, Baum A, Guth B, Colbatzky F, Blech S, Amelsberg A, Himmelsbach F (2005) BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor for cancer therapy. Proceedings, AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Philadelphia, PA. 14–18 November 2005:118 (Abstract A244)
76.
go back to reference Solca F, Schweifer N, Baum A, Rudolph D, Amelsberg A, Himmelsbach F, Beug H (2005) BIBW 2992, an irreversible dual EGFR/HER2 kinase inhibitor, shows activity on L858R/T790M EGFR mutants. Clin Cancer Res 11(23):A242 Solca F, Schweifer N, Baum A, Rudolph D, Amelsberg A, Himmelsbach F, Beug H (2005) BIBW 2992, an irreversible dual EGFR/HER2 kinase inhibitor, shows activity on L858R/T790M EGFR mutants. Clin Cancer Res 11(23):A242
77.
go back to reference Shimamura T, Gewulich H, Solca F, Wong K (2007) Efficacy of BIBW 2992, a potent irreversible inhibitor of EGFR and HER2 in human NSCLC xenografts and in a transgenic mouse lung-cancer model. Journal of Thoracic Oncology 2(8):380CrossRef Shimamura T, Gewulich H, Solca F, Wong K (2007) Efficacy of BIBW 2992, a potent irreversible inhibitor of EGFR and HER2 in human NSCLC xenografts and in a transgenic mouse lung-cancer model. Journal of Thoracic Oncology 2(8):380CrossRef
78.
go back to reference Li D, Shimamura T, Ji H, Chen L, Haringsma HJ, McNamara K, Liang MC, Perera SA, Zaghlul S, Borgman CL, Kubo S, Takahashi M, Sun Y, Chirieac LR, Padera RF, Lindeman NI, Janne PA, Thomas RK, Meyerson ML, Eck MJ, Engelman JA, Shapiro GI, Wong KK (2007) Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell 12(1):81–93CrossRefPubMed Li D, Shimamura T, Ji H, Chen L, Haringsma HJ, McNamara K, Liang MC, Perera SA, Zaghlul S, Borgman CL, Kubo S, Takahashi M, Sun Y, Chirieac LR, Padera RF, Lindeman NI, Janne PA, Thomas RK, Meyerson ML, Eck MJ, Engelman JA, Shapiro GI, Wong KK (2007) Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell 12(1):81–93CrossRefPubMed
79.
go back to reference Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong KK (2009) HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A 106(2):474–479CrossRefPubMed Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong KK (2009) HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A 106(2):474–479CrossRefPubMed
80.
go back to reference Plummer R, Vidal L, Perrett R, Spicer J, Stopfer P, Shahidi M, Temple G, Futreal A, Calvert H, de Bono J (2007) A Phase I and pharmacokinetic (PK) study of BIBW 2992, an oral irreversible dual EGFR/HER2 inhibitor. Eur J Cancer Suppl 5(4):108CrossRef Plummer R, Vidal L, Perrett R, Spicer J, Stopfer P, Shahidi M, Temple G, Futreal A, Calvert H, de Bono J (2007) A Phase I and pharmacokinetic (PK) study of BIBW 2992, an oral irreversible dual EGFR/HER2 inhibitor. Eur J Cancer Suppl 5(4):108CrossRef
81.
go back to reference Spicer J, Calvert H, Vidal L, Azribi F, Perrett R, Shahidi M, Temple G, Futreal A, De Bono J, Plummer R (2007) Activity of BIBW2992, an oral irreversible dual EGFR/HER2 inhibitor, in non-small cell lung cancer (NSCLC) with mutated EGFR. J Thor Oncol 2(8):S410CrossRef Spicer J, Calvert H, Vidal L, Azribi F, Perrett R, Shahidi M, Temple G, Futreal A, De Bono J, Plummer R (2007) Activity of BIBW2992, an oral irreversible dual EGFR/HER2 inhibitor, in non-small cell lung cancer (NSCLC) with mutated EGFR. J Thor Oncol 2(8):S410CrossRef
82.
go back to reference Eskens FA, Mom CH, Planting AS, Gietema JA, Amelsberg A, Huisman H, van Doorn L, Burger H, Stopfer P, Verweij J, de Vries EG (2008) 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 98(1):80–85CrossRefPubMed Eskens FA, Mom CH, Planting AS, Gietema JA, Amelsberg A, Huisman H, van Doorn L, Burger H, Stopfer P, Verweij J, de Vries EG (2008) 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 98(1):80–85CrossRefPubMed
83.
go back to reference Agus DB, Terlizzi E, Stopfer P, Amelsberg A, Gordon MS (2006) 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 tumours. J Clin Oncol 24(18S):Abstract 2074 Agus DB, Terlizzi E, Stopfer P, Amelsberg A, Gordon MS (2006) 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 tumours. J Clin Oncol 24(18S):Abstract 2074
84.
go back to reference Lewis N, Marshall J, Amelsberg A, Cohen RB, Stopfer P, Hwang J, Malik S (2006) A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a 3 week on 1week off schedule in patients with advanced solid tumours. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings. Part I. 24(18S (June 20 supplement)):Abstract 3091 Lewis N, Marshall J, Amelsberg A, Cohen RB, Stopfer P, Hwang J, Malik S (2006) A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a 3 week on 1week off schedule in patients with advanced solid tumours. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings. Part I. 24(18S (June 20 supplement)):Abstract 3091
85.
go back to reference Shaw H, Plummer R, Vidal L, Perrett R, Pilkington M, Temple G, Fong P, Amelsberg A, Calvert H, de Bono J (2006) A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in patients with advanced solid tumours. J Clin Oncol 24(18S):3027 Shaw H, Plummer R, Vidal L, Perrett R, Pilkington M, Temple G, Fong P, Amelsberg A, Calvert H, de Bono J (2006) A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in patients with advanced solid tumours. J Clin Oncol 24(18S):3027
86.
go back to reference Stopfer P, Schaefer HG, Amelsberg A, Huisman H, Eskens F, Gietema JA, Briscoe J, Lewis N, Cohen RB, Marshall J, Verweij J (2005) 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 tumours. Proceedings, AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics:171(Abstract B172) Stopfer P, Schaefer HG, Amelsberg A, Huisman H, Eskens F, Gietema JA, Briscoe J, Lewis N, Cohen RB, Marshall J, Verweij J (2005) 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 tumours. Proceedings, AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics:171(Abstract B172)
87.
go back to reference Shih JY, Yang CH, Su WC, Hsia TC, Tsai CM, Chen YM, Chang H, Terlizzi E, Shahidi M, Miller VA (2009) 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 1 line of chemotherapy (LUX-Lung 2). J Clin Oncol 27 (Suppl 15):Abstract 8013 Shih JY, Yang CH, Su WC, Hsia TC, Tsai CM, Chen YM, Chang H, Terlizzi E, Shahidi M, Miller VA (2009) 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 1 line of chemotherapy (LUX-Lung 2). J Clin Oncol 27 (Suppl 15):Abstract 8013
88.
go back to reference ClinicalTrials.gov (2008) BIBW 2992 (TOVOK) and BSC versus placebo and BSC in non-small cell lung cancer patients failing erlotinib or gefitinib (LUX-LUNG 1). Available from: www.clinicalstrial.gov. Cited Dec 4, 2008 ClinicalTrials.gov (2008) BIBW 2992 (TOVOK) and BSC versus placebo and BSC in non-small cell lung cancer patients failing erlotinib or gefitinib (LUX-LUNG 1). Available from: www.​clinicalstrial.​gov. Cited Dec 4, 2008
89.
go back to reference De Greve J, Teugels E, Geers C, De Mey J, In’t Veld P, Decoster L, Taton M, Shahidi M, Galdermans D, Schallier D (2009) Activity of BIBW 2992, an irreversible inhibitor of EGFR and HER2, in adenocarcinoma of the lung with HER2neu kinase domain mutations. Eur J Cancer Suppl 7(2):555CrossRef De Greve J, Teugels E, Geers C, De Mey J, In’t Veld P, Decoster L, Taton M, Shahidi M, Galdermans D, Schallier D (2009) Activity of BIBW 2992, an irreversible inhibitor of EGFR and HER2, in adenocarcinoma of the lung with HER2neu kinase domain mutations. Eur J Cancer Suppl 7(2):555CrossRef
90.
91.
go back to reference Wong KK, Fracasso PM, Bukowski RM, Munster PN, Lynch T, Abbas R, Quinn SE, Zacharchuk C, Burris H (2006) HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase 1 results in patients with solid tumors. J Clin Oncol 24(18S):3018 Wong KK, Fracasso PM, Bukowski RM, Munster PN, Lynch T, Abbas R, Quinn SE, Zacharchuk C, Burris H (2006) HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase 1 results in patients with solid tumors. J Clin Oncol 24(18S):3018
92.
go back to reference Yoshimura N, Kudoh S, Kimura T, Mitsuoka S, Matsuura K, Hirata K, Matsui K, Negoro S, Nakagawa K, Fukuoka M (2006) 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 51(3):363–368CrossRefPubMed Yoshimura N, Kudoh S, Kimura T, Mitsuoka S, Matsuura K, Hirata K, Matsui K, Negoro S, Nakagawa K, Fukuoka M (2006) 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 51(3):363–368CrossRefPubMed
Metadata
Title
EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992
Authors
James F. Spicer
Sarah M. Rudman
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Targeted Oncology / Issue 4/2010
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-010-0140-y

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