진행성 비소세포폐암의 표적치료 및 맞춤항암치료
Targeted therapy and tailored chemotherapy for advanced non-small cell lung cancer
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초록
The prognosis of advanced non-small cell lung cancer (NSCLC) is very poor and the median overall survival is 10 to 12 months, despite the use of chemotherapy and targeted therapy. Recently, many targeted agents for NSCLC have been developed and tested in clinical trials. Of these, chemotherapeutic agents targeting epidermal growth factor receptor (EGFR), such as gefitinib, erlotinib and cetuximab, have been very efficacious in the treatment of NSCLC. Many phase III trials have evaluated the efficacy of these agents in combination with cytotoxic chemotherapy. Based on the results of these trials, clinical and molecular predictors of the response to EGFR-targeted agents, such as EGFR mutations or gene amplification, have been elucidated. Recent advances in understanding the biologic basis of acquired resistance to these agents have potential to improve the clinical effectiveness of agents targeting EGFR. Another agent, bevacizumab, targets an angiogenesis inhibitor, and has improved the survival in advanced NSCLC when used in combination with chemotherapy. In addition, many agents targeting tyrosine kinase inhibitors are being used in clinical trials. This review summarizes the outcomes of clinical trials evaluating agents targeting EGFR, angiogenesis inhibitors, and other molecules used alone or in combination with chemotherapy for the treatment of advanced NSCLC. Also, the predictive role of NSCLC histology for chemotherapy response will be summarized from the results of phase III studies.
Abstract
The prognosis of advanced non-small cell lung cancer (NSCLC) is very poor and the median overall survival is 10 to 12 months, despite the use of chemotherapy and targeted therapy. Recently, many targeted agents for NSCLC have been developed and tested in clinical trials. Of these, chemotherapeutic agents targeting epidermal growth factor receptor (EGFR), such as gefitinib, erlotinib and cetuximab, have been very efficacious in the treatment of NSCLC. Many phase III trials have evaluated the efficacy of these agents in combination with cytotoxic chemotherapy. Based on the results of these trials, clinical and molecular predictors of the response to EGFR-targeted agents, such as EGFR mutations or gene amplification, have been elucidated. Recent advances in understanding the biologic basis of acquired resistance to these agents have potential to improve the clinical effectiveness of agents targeting EGFR. Another agent, bevacizumab, targets an angiogenesis inhibitor, and has improved the survival in advanced NSCLC when used in combination with chemotherapy. In addition, many agents targeting tyrosine kinase inhibitors are being used in clinical trials. This review summarizes the outcomes of clinical trials evaluating agents targeting EGFR, angiogenesis inhibitors, and other molecules used alone or in combination with chemotherapy for the treatment of advanced NSCLC. Also, the predictive role of NSCLC histology for chemotherapy response will be summarized from the results of phase III studies.
참고문헌 (39)
- Parkin DM, "Global cancer statistics, 2002", CA Cancer J Clin, 55, pp.74~108 (2005)
- Schiller JH, "Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer", N Engl J Med, 346, pp.92~98 (2002)
- Lynch TJ, "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib", N Engl J Med, 350, pp.2129~2139 (2004)
- Kris MG, "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, pp.2149~2158 (2003)
- "J Clin Oncol", 2003, 2237~2246
- Giaccone G, "Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial: INTACT 1", J Clin Oncol, 22, pp.777~784 (2004)
- Herbst RS, "Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial: INTACT 2", J Clin Oncol, 22, pp.785~794 (2004)
- Kim ES, "Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial", Lancet, 372, pp.1809~1818 (2008)
- Shepherd FA, "Erlotinib in previously treated non-small-cell lung cancer", N Engl J Med, 353, pp.123~132 (2005)
- Herbst RS, "TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer", J Clin Oncol, 23, pp.5892~5899 (2005)
- Gatzemeier U, "Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-smallcell lung cancer: the Tarceva Lung Cancer Investigation Trial", J Clin Oncol, 25, pp.1545~1552 (2007)
- Hirsch FR, "Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer", J Clin Oncol, 24, pp.5034~5042 (2006)
- Sequist LV, "Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer", J Clin Oncol, 25, pp.587~595 (2007)
- Kim TY, "Chasing targets for EGFR tyrosine kinase inhibitors in non-small-cell lung cancer: Asian perspectives", Expert Rev Mol Diagn, 7, pp.821~836 (2007)
- Engelman JA, "MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling", Science, 316, pp.1039~1043 (2007)
- Giaccone G, "EGFR point mutation confers resistance to gefitinib in a patient with non-small-cell lung cancer", Nat Clin Pract Oncol, 2, pp.296~297 (2005)
- Engelman JA, "PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib", Cancer Res, 67, pp.11924~11932 (2007)
- Li D, "BIBW2992, an irreversible EGFR", HER2 inhibitor highly effective in preclinical lung cancer models, 2008, pp.27, 4702~4711
- Rossi A, "Cetuximab in advanced non-small cell lung cancer", Crit Rev Oncol Hematol, 59, pp.139~149 (2006)
- Bonner JA, "Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck", N Engl J Med, 354, pp.567~578 (2006)
- , with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer, "J Clin Oncol", 2007, 5777~5784
- Pirker R, "Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial", Lancet, 373, pp.1525~1531 (2009)
- Herbst RS, "Non-small cell lung cancer and antiangiogenic therapy: what can be expected of bevacizumab?", Oncologist, 9(1), pp.19~26 (2004)
- Eskens FA, "The use of bevacizumab in colorectal, lung, breast, renal and ovarian cancer: where does it fit?", Eur J Cancer, 44, pp.2350~2356 (2008)
- Johnson DH, "Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer", J Clin Oncol, 22, pp.2184~2191 (2004)
- Sandler A, "Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer", N Engl J Med, 355, pp.2542~2550 (2006)
- Reck M, "Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-smallcell lung cancer: AVAil", J Clin Oncol, 27, pp.1227~1234 (2009)
- Gridelli C, "Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer", Oncologist, 12, pp.191~200 (2007)
- Blumenschein G Jr, "Sorafenib in lung cancer: clinical developments and future directions", J Thorac Oncol, 3, pp.S124~S127 (2008)
- Socinski MA, "Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer", J Clin Oncol, 26, pp.650~656 (2008)
- Natale RB, "Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase II study", J Clin Oncol, 27, pp.2523~2529 (2009)
- Heymach JV, "Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer", J Clin Oncol, 25, pp.4270~4277 (2007)
- Morgillo F, "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, 13, pp.2795~2803 (2007)
- Karp DD, "Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer", J Clin Oncol, 27, pp.2516~2522 (2009)
- Hanna N, "Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small- cell lung cancer previously treated with chemotherapy", J Clin Oncol, 22, pp.1589~1597 (2004)
- Scagliotti G, "The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies", Oncologist, 14, pp.253~263 (2009)
- Scagliotti GV, "Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer", J Clin Oncol, 26, pp.3543~3551 (2008)
- Olaussen KA, "IALT Bio Investigators. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy", N Engl J Med, 355, pp.983~991 (2006)
- Cobo M, "Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer", J Clin Oncol, 25, pp.2747~2754 (2007)
