Afatinib – nová perspektiva u nemalobuněčného karcinomu plic

Číslo: 2 / 2011 (Obsah)
Rubrika: Profily léčiv
Obor: Onkologie
Autoři: MUDr. Lenka Babičková, Ph.D.
Autoři - působiště: Klinika nemocí plicních a tuberkulózy LF MU a FN, Brno
Klíčová slova: afatinib, nemalobuněčný karcinom plic, blokátory tyrosinkinázy receptoru pro epidermální růstový faktor (EGFR)
Citace: 1 Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005;23:8081–92. 2 Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39. 3 Mok T, Wu Y-L, Thongprasert S, et al. 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. 4 Greulich H, Chen TH, Feng W, et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med 2005;2:e313. 5 Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008;359:366–77. 6 Herbst RS, Heymach LV, Lippman SM. Lung Cancer. N Engl J Med 2008;359:1367–70. 7 Shih JY, Gow CH, Yang PC. EGFR mutation conferring primary resistance to gefitinib in non-small cell lung cancer. N Engl J Med 2005;353:207–8. 8 Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17. 9 Miller VA, Zakowski M, Riely GJ, et al. EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): results of  perspective phase II trial (abstract no. 7003). J Clin Oncol 2006;24:364s. 10 Tsao M, Zhu C, Sakurada A, et al. An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer (abstract no. 7005). J Clin Oncol 2006;24:365s. 11 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 2007;104:20932–7. 12 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 2006;12:6494–501. 13 Kosaka T, Yatabe Y, Endoh H, et al. 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;12:5764–9. 14 Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73. 15 Kumar A, Petri ET, Halmos B, et al. Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 2008;26:1742–51. 16 Wood ER, Truesdale AT, McDonald OB, et al. A unique structure for epidermal growth factor receptor bound to GW572016 (lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res 2004;64:6652–9. 17 Jiang SX, Yamashita K, Yamamoto M, et al. EGFR genetic heterogeneity of non-small cell lung cancers contributing to acquired gefitinib resistance. Int J Cancer 2008;123:2480–6. 18 Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signalling. Science 2007;316:1039–43. 19 Belani CP. The role of irreversible EGFR inhibitors in the treatment of non-small cell lung cancer: overcoming resistance to reversible EGFR inhibitors. Cancer Invest 2010;28:413–23. 20 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 2008;98:80–5. 21 Agus D, Terlizzi E, Stopfer P, et al. 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. 22 Stopfer P, Schaefer H, Amelsberg A, et al. 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. 23 BIBW 2992 and BSC versus placebo and BSC in non-small cell 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. 24 Yang C, Hirsh V, Cadranel J, et al. 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. 25 Shih J, Yang C, Su WC, et al. 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. 26 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.

Souhrn

Ve snaze ovlivnit špatnou prognózu a dosud neuspokojivé výsledky léčby u nemocných s metastazujícím a lokoregionálně pokročilým nemalobuněčným karcinomem plic jsou vyvíjeny a klinicky testovány další léky, k nimž patří i nová malá molekula k perorálnímu podávání afatinib (BIBW 2992) s duálním účinkem spočívajícím v ireverzibilní blokádě EGFR i HER2. Dosud jsou známy výsledky preklinických studií a studie II. a II./III. fáze, další testování probíhá. Dosavadní výsledky a závěry jsou uvedeny v tomto článku. „

Literatura

1 Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005;23:8081–92. 2 Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39. 3 Mok T, Wu Y-L, Thongprasert S, et al. 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. 4 Greulich H, Chen TH, Feng W, et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med 2005;2:e313. 5 Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008;359:366–77. 6 Herbst RS, Heymach LV, Lippman SM. Lung Cancer. N Engl J Med 2008;359:1367–70. 7 Shih JY, Gow CH, Yang PC. EGFR mutation conferring primary resistance to gefitinib in non-small cell lung cancer. N Engl J Med 2005;353:207–8. 8 Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17. 9 Miller VA, Zakowski M, Riely GJ, et al. EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): results of  perspective phase II trial (abstract no. 7003). J Clin Oncol 2006;24:364s.
10
Tsao M, Zhu C, Sakurada A, et al. An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer (abstract no. 7005). J Clin Oncol 2006;24:365s.
11
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 2007;104:20932–7.
12
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 2006;12:6494–501.
13
Kosaka T, Yatabe Y, Endoh H, et al. 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;12:5764–9.
14
Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73.
15
Kumar A, Petri ET, Halmos B, et al. Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol 2008;26:1742–51.
16
Wood ER, Truesdale AT, McDonald OB, et al. A unique structure for epidermal growth factor receptor bound to GW572016 (lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res 2004;64:6652–9.
17
Jiang SX, Yamashita K, Yamamoto M, et al. EGFR genetic heterogeneity of non-small cell lung cancers contributing to acquired gefitinib resistance. Int J Cancer 2008;123:2480–6.
18
Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signalling. Science 2007;316:1039–43.
19
Belani CP. The role of irreversible EGFR inhibitors in the treatment of non-small cell lung cancer: overcoming resistance to reversible EGFR inhibitors. Cancer Invest 2010;28:413–23.
20
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 2008;98:80–5.
21
Agus D, Terlizzi E, Stopfer P, et al. 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.
22
Stopfer P, Schaefer H, Amelsberg A, et al. 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.
23
BIBW 2992 and BSC versus placebo and BSC in non-small cell 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.
24
Yang C, Hirsh V, Cadranel J, et al. 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.
25
Shih J, Yang C, Su WC, et al. 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.
26
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.

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