The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer

Expert Review of Anticancer Therapy

Volumn 11, Issue 5, 2011, Pages 673-682

  Metro, Giulio ^a   Crinò, Lucio ^a  

^a S Maria Della Misericordia General Hospital   (Italy)

Author keywords

afatinib; clinical resistance; epidermal growth factor receptor; erlotinib; gefitinib; LUX Lung clinical trial program; non small cell lung cancer; tyrosine kinase inhibitors

Indexed keywords

AFATINIB; ERLOTINIB; GEFITINIB; PLACEBO; VASCULOTROPIN RECEPTOR;

ACNE; ADVANCED CANCER; ARTICLE; CANCER RESISTANCE; CANCER STAGING; CANCER SURVIVAL; DECREASED APPETITE; DIARRHEA; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG INDICATION; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; EPISTAXIS; GENE MUTATION; GENE TARGETING; HUMAN; LUNG ADENOCARCINOMA; LUNG CANCER; LUNG NON SMALL CELL CANCER; NAIL DISEASE; OVERALL SURVIVAL; PNEUMONIA; PROGRESSION FREE SURVIVAL; PRURITUS; RASH; STOMATITIS; TREATMENT DURATION; TREATMENT OUTCOME;

ADENOCARCINOMA; ADULT; AGED; AGED, 80 AND OVER; CARCINOMA, NON-SMALL-CELL LUNG; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; MIDDLE AGED; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; TREATMENT OUTCOME;

EID: 79955853698     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.11.34     Document Type: Article

References (59)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J. Clin. 60(5), 277-300 (2010).
2. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur. J. Cancer 46(4), 765-781 (2010).
3. Ramalingam S, Belani C. Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions. Oncologist 13(Suppl. 1), 5-13 (2008).
4. Sandler A, Gray R, Perry MC et al Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355(24), 2542-2550 (2006).
5. Pirker R, Pereira JR, Szczesna A et al Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised Phase III trial. Lancet 373(9674), 1525-1531 (2009).
6. Metro G, Cappuzzo F. New targeted therapies for non-small-cell lung cancer. Therapy 6(3), 335-350 (2009).
7. Kwak EL, Bang YJ, Camidge DR et al Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363(18), 1693-1703(2010).
8. Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin. Oncol. 33(4), 369-385 (2006).
9. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7(3), 169-181 (2007).
10. Paez JG, Janne PA, Lee JC et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy Science 304(5676), 1497-1500 (2004).
11. 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. 350(21), 2129-2139 (2004).
12. 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. USA 101(36), 13306-13311 (2004).
13. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclkaxel in pulmonary adenocarcinoma. N. Engl J. Med. 361(10), 947-957 (2009).
14. Lee JS, Park K, Kim SW et al. A randomized Phase III study of gefitinib (IRESSA™) versus standard chemotherapy (gemcitabine plus cispladn) as a first-line treatment for never-smokers with advanced or metastatic adenocarcinoma of the lung J. Thor. Oncol. 4(Suppl.), 4 (2009) (Abstract).
15. Mitsudomi T, Morita S, Yatabe Y et al Gefitinib versus cispladn plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 11(2), 121-128 (2010).
16. Maemondo M, Inoue A, Kobayashi K et al Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl. J. Med. 362(25), 2380-2388 (2010).
17. Zhou C, Wu YL, Chen G et al. Efficacy results from the randomised Phase III OPTIMAL (CTONG 0802) study comparing first-line erlotinib versus carbopladn plus gemcitabine, in chinese advanced non-small-cell lung cancer patients with EGFR activating mutations. Ann. Oncol. 21(Suppl. 8), LBA 13 (2010).
18. Mitsudomi T, Kosaka T, Yatabe Y. Biological and clinical implications of EGFR mutations in lung cancer. Int. J.Clin. Oncol. 11(3), 190-198 (2006).
19. Rosell R, Moran T, Queralt C et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361(10), 958-967 (2009).
20. Murray S, Dahabreh IJ, Linardou H, Manoloukos M, Bafaloukos D, Kosmidis P. Somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor and tyrosine kinase inhibitor response to TKIs in non-small cell lung cancer: an analytical database. J. Thorac. Oncol. 3(8), 832-839 (2008).
21. 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. 12(13), 3908-3914 (2006).
22. Paz-Ares L, Soulieres D, Melezinek I et al. Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis. J. CellMol. Med. 14(1-2), 51-69 (2010).
23. Greulich H, Chen TH, Feng W et al. Oncogenic transformation by inhibitor-sensitive and - resistant EGFR mutants. PloSMed. 2(11), e313 (2005).
24. Wu JY, Wu SG, Yang CH et al. Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin. Cancer Res. 14(15), 4877-4882 (2008).
25. Kobayashi S, Boggon TJ, Dayaram T et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352(8), 786-792 (2005).
26. 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. PloSMed. 2(3), e73 (2005).
27. Balak MN, Gong Y, Riely GJ et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin. Cancer Res. 12(21), 6494-6501 (2006).
28. Maheswaran S, Sequist LV, Nagrath S et al. Detection of mutations in EGFR in circulating lung-cancer cells. N. Engl. J. Med. 359(4), 366-377 (2008).
29. Bean J, Riely GJ, Balak M et al. Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin. Cancer Res. 14(22), 7519-7525 (2008).
30. Engelman JA, Zejnullahu K, Mitsudomi T et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316(5827), 1039-1043 (2007).
31. Bean J, Brennan C, Shih JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl Acad. Sci. USA 104(52), 20932-20937 (2007).
32. Oxnard GR, Arcila ME, Sima C et al. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR mutant lung cancer: Distinct natural history of patients with tumors harboring the T790M mutation. Clin. Cancer Res. 17(6), 1616-1622 (2011).
33. Li D, Ambrogio L, SltimamuraT et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27'(34), 4702-4711 (2008).
34. Yap TA, Vidal L, Adam J et al. Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J. Clin. Oncol. 28(25), 3965-3972(2010).
35. Lewis N, Marshall J, Amelsberg A et al. 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. Proc. Am. Soc. Clin. Oncol. 24(Suppl. 18), 3091 (2006) (Abstract).
36. Agus DB, Terlizzi E, Stopfer P, Amelsberg A, Gordon MS. 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. Proc. Am. Soc. Clin. Oncol. 24(Suppl. 18), 2074 (2006) (Abstract).
37. Eskens FA, Mom CH, Planting AS et al. 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), 80-85 (2008).
38. Miller VA, Hirsh V, Cadranei J et al. Phase IIB/III double-blind randomized trial of afatinib (BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2) + best supportive care (BSC) versus placebo in patients with NSCLC failing 1-2 lines of chemotherapy and erlotinib or gefitinib (LUX-LUNG I). Ann. Oncol. 21(Suppl. 8), LBA 1 (2010) (Abstract).
39. Miller VA, Hirsh V, Cadranei J et al. Subgroup analysis of LUX-Lung 1: a randomized Phase III trial of afatinib (BIBW 2992) + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1-2 lines of chemotherapy and erlotinib or gefitinib. Presented at: 2010 Chicago Multidisciplinary Symposium in Thoracic Oncology. Chicago, IL, USA, 9-11 December 2010.
40. Yang CH, Shih JY, Su WC et al. A Phase II of afatinib (BIBW 2992) in patients with adenocarcinoma of the lung and activating EGFR mutations. Ann. Oncol. 21(Suppl. 8), 367 (2010) (Abstract).
41. Shih JY, Yu CJ, Su WC et al. Activity of afatinib (BIBW2992) an irreversible EGFR/HER1 and HER2 TKI, in lung adenocarcinoma patients harbouring less common EGFR/HER1 mutations. Ann. Oncol. 21(Suppl. 8), 415 (2010) (Abstract).
42. Jackman D, Pao W, Riely GJ et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J. Clin. Oncol. 28(2), 357-360 (2010).
43. Riely GJ, Kris MG, Zhao B et al. Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or geftinib followed by the addition of everolimus. Clin. Cancer Res. 13(17), 5150-5155 (2007).
44. Costa DB, Nguyen KS, Cho BC, et al. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to geftinib. Clin. Cancer Res. 14(21), 7060-7067 (2008).
45. Broglio KR, Berry DA. Detecting an overall survival beneft that is derived from progression-free survival. J. Natl Cancer Inst. 101(23), 1642-1649 (2009).
46. Kwak EL, Sordella R, Bell DW et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to geftinib. Proc. Natl Acad. Sci. USA 102(21), 7665-7670 (2005).
47. Asahina H, Yamazaki K, Kinoshita I et al. A Phase II trial of geftinib as frst-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. Br. J. Cancer 95(8), 998-1004 (2006).
48. Inoue A, Kobayashi K, Usui K et al. First-line geftinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J. Clin. Oncol. 27(9), 1394-1400 (2009).
49. Inoue A, Suzuki T, Fukuhara T et al. Prospective Phase II study of geftinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J. Clin. Oncol. 24(21), 3340-3346 (2006).
50. Rosell R, Perez-Roca L, Sanchez JJ et al. Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression. PLoS One 4(5), e5133 (2009).
51. Sequist LV, Martins RG, Spigel D et al. First-line geftinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J. Clin. Oncol. 26(15), 2442-2449 (2008).
52. Yang CH, Yu CJ, Shih JY et al. Specifc EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving frst-line geftinib monotherapy. J. Clin. Oncol. 26(16), 2745-2753 (2008).
53. Sugio K, Uramoto H, Onitsuka et al. Prospective Phase II study of geftinib in non-small cell lung cancer with epidermal growth factor receptor gene mutations. Lung Cancer 64(3), 314-318 (2009).
54. Sunaga N, Tomizawa Y, Yanagitani N et al. Phase II prospective study of the effcacy of geftinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy. Lung Cancer 56(3), 383-389 (2007).
55. Sutani A, Nagai Y, Udagawa K et al. Geftinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp. Br. J. Cancer 95(11), 1483-1489 (2006).
56. Yoshida K, Yatabe Y, Park J et al. Prospective validation for prediction of geftinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer. J. Thorac. Oncol. 2(1), 22-28 (2007).
57. 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 geftinib. J. Clin. Oncol. 23(11), 2493-2501 (2005).
58. Tamura K, Okamoto I, Kashii T et al. Multicentre prospective Phase II trial of geftinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403). Br. J. Cancer 98(5), 907-914 (2008).
59. Regales L, Gong Y, Shen R et al. Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J. Clin. Invest. 119(10), 3000-3010 (2009).