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Erschienen in: Cancer Chemotherapy and Pharmacology 1/2015

01.01.2015 | Original Article

EGFR–TKI is effective regardless of treatment timing in pulmonary adenocarcinoma with EGFR mutation

verfasst von: Dong-Hoe Koo, Kyu-pyo Kim, Chang-Min Choi, Dae-Ho Lee, Jae Cheol Lee, Jung-Shin Lee, Se Jin Jang, Sang-We Kim

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2015

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Abstract

Purpose

Although epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) have become key therapeutic agents for non-small cell lung cancer (NSCLC) patients with EGFR mutation, little is known about the efficacy of EGFR–TKIs according to different treatment timings.

Methods

A total of 1,250 patients with NSCLC were screened for EGFR mutations at a single institution between March 2006 and May 2010. The efficacy of EGFR–TKIs in terms of response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared according to the treatment timing.

Results

Among the 437 patients (36.1 %) with EGFR mutation, we analyzed 222 patients who received EGFR–TKI treatment. With a median follow-up duration of 27.5 months (range 8.3–69.2), EGFR–TKI was given to 97 (43.7 %), 109 (49.1 %), and 16 (7.2 %) patients as first-line, second-line, and third-line therapy, respectively. All three groups showed similar RR (71.1, 72.5, and 75.0 %, respectively) to EGFR–TKI (p = 0.802). No significant difference was observed according to treatment timing of EGFR–TKI in terms of PFS (median 10.6, 13.0, and 10.4 months; p = 0.670) and OS (median 20.5, 26.2, and 17.1 months; p = 0.142). The treatment timing of EGFR–TKI still showed no association with PFS or OS after adjusting significant prognostic factors including performance, disease status, and EGFR mutation types.

Conclusions

EGFR–TKIs showed similar efficacy in patients with EGFR mutation-positive adenocarcinoma in terms of RR, PFS, and OS irrespective of treatment timing. Although EGFR–TKIs are currently the treatment of choice of first-line treatment in patients with EGFR-positive tumors, the sequential treatment with EGFR–TKI could be a reasonable option when EGFR mutation status cannot be obtained in a short time.
Literatur
1.
Zurück zum Zitat Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246PubMedCrossRef Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246PubMedCrossRef
2.
Zurück zum Zitat 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, Santabárbara P, Seymour L (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132PubMedCrossRef 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, Santabárbara P, Seymour L (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132PubMedCrossRef
3.
Zurück zum Zitat Novello S, Pimentel FL, Douillard JY, O’Brien M, von Pawel J, Eckardt J, Liepa AM, Simms L, Visseren-Grul C, Paz-Ares L (2010) Safety and resource utilization by non-small cell lung cancer histology: results from the randomized phase III study of pemetrexed plus cisplatin versus gemcitabine plus cisplatin in chemonaive patients with advanced non-small cell lung cancer. J Thorac Oncol 5:1602–1608PubMedCrossRef Novello S, Pimentel FL, Douillard JY, O’Brien M, von Pawel J, Eckardt J, Liepa AM, Simms L, Visseren-Grul C, Paz-Ares L (2010) Safety and resource utilization by non-small cell lung cancer histology: results from the randomized phase III study of pemetrexed plus cisplatin versus gemcitabine plus cisplatin in chemonaive patients with advanced non-small cell lung cancer. J Thorac Oncol 5:1602–1608PubMedCrossRef
4.
Zurück zum Zitat Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar J-S, Squire J, Thunnissen E, Ladanyi M (2013) Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn 15:415–453PubMedCrossRef Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar J-S, Squire J, Thunnissen E, Ladanyi M (2013) Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn 15:415–453PubMedCrossRef
5.
Zurück zum Zitat Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12:735–742PubMedCrossRef Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12:735–742PubMedCrossRef
6.
Zurück zum Zitat Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388PubMedCrossRef Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388PubMedCrossRef
7.
Zurück zum Zitat Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang J-J, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957PubMedCrossRef Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang J-J, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957PubMedCrossRef
8.
Zurück zum Zitat Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E (2012) Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii56–vii64PubMedCrossRef Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E (2012) Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii56–vii64PubMedCrossRef
9.
Zurück zum Zitat Ellis S, Carroll KJ, Pemberton K (2008) Analysis of duration of response in oncology trials. Contemp Clin Trials 29:456–465PubMedCrossRef Ellis S, Carroll KJ, Pemberton K (2008) Analysis of duration of response in oncology trials. Contemp Clin Trials 29:456–465PubMedCrossRef
10.
Zurück zum Zitat 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, The Spanish Lung Cancer Group (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361:958–967PubMedCrossRef 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, The Spanish Lung Cancer Group (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361:958–967PubMedCrossRef
11.
Zurück zum Zitat Eberhard DA, Giaccone G, Johnson BE (2008) Biomarkers of response to epidermal growth factor receptor inhibitors in non-small-cell lung cancer working group: standardization for use in the clinical trial setting. J Clin Oncol 26:983–994PubMedCrossRef Eberhard DA, Giaccone G, Johnson BE (2008) Biomarkers of response to epidermal growth factor receptor inhibitors in non-small-cell lung cancer working group: standardization for use in the clinical trial setting. J Clin Oncol 26:983–994PubMedCrossRef
12.
Zurück zum Zitat Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M (2010) Gefitinib versus cisplatin 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 11:121–128PubMedCrossRef Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M (2010) Gefitinib versus cisplatin 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 11:121–128PubMedCrossRef
13.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRef
14.
Zurück zum Zitat Inoue A, Suzuki T, Fukuhara T, Maemondo M, Kimura Y, Morikawa N, Watanabe H, Saijo Y, Nukiwa T (2006) Prospective phase II study of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 24:3340–3346PubMedCrossRef Inoue A, Suzuki T, Fukuhara T, Maemondo M, Kimura Y, Morikawa N, Watanabe H, Saijo Y, Nukiwa T (2006) Prospective phase II study of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 24:3340–3346PubMedCrossRef
15.
Zurück zum Zitat Sunaga N, Tomizawa Y, Yanagitani N, Iijima H, Kaira K, Shimizu K, Tanaka S, Suga T, Hisada T, Ishizuka T, Saito R, Dobashi K, Mori M (2007) Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy. Lung Cancer 56:383–389PubMedCrossRef Sunaga N, Tomizawa Y, Yanagitani N, Iijima H, Kaira K, Shimizu K, Tanaka S, Suga T, Hisada T, Ishizuka T, Saito R, Dobashi K, Mori M (2007) Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy. Lung Cancer 56:383–389PubMedCrossRef
16.
Zurück zum Zitat Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12:175–180PubMedCrossRef Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12:175–180PubMedCrossRef
17.
Zurück zum Zitat Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98PubMedCrossRef Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98PubMedCrossRef
18.
Zurück zum Zitat Fukuoka M, Wu Y-L, Thongprasert S, Sunpaweravong P, Leong S-S, Sriuranpong V, Chao T-Y, Nakagawa K, Chu D-T, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To K-F, Yang JC-H, Mok TSK (2011) Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 29:2866–2874PubMedCrossRef Fukuoka M, Wu Y-L, Thongprasert S, Sunpaweravong P, Leong S-S, Sriuranpong V, Chao T-Y, Nakagawa K, Chu D-T, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To K-F, Yang JC-H, Mok TSK (2011) Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 29:2866–2874PubMedCrossRef
20.
Zurück zum Zitat Zhou Q, Zhang X-C, Chen Z-H, Yin X-L, Yang J-J, Xu C-R, Yan H-H, Chen H-J, Su J, Zhong W-Z, Yang X-N, An S-J, Wang B-C, Huang Y-S, Wang Z, Wu Y-L (2011) Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol 29:3316–3321PubMedCrossRef Zhou Q, Zhang X-C, Chen Z-H, Yin X-L, Yang J-J, Xu C-R, Yan H-H, Chen H-J, Su J, Zhong W-Z, Yang X-N, An S-J, Wang B-C, Huang Y-S, Wang Z, Wu Y-L (2011) Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol 29:3316–3321PubMedCrossRef
21.
Zurück zum Zitat Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550PubMedCrossRef Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550PubMedCrossRef
22.
Zurück zum Zitat Wu J-Y, Yu C-J, Yang C-H, Wu S-G, Chiu Y-H, Gow C-H, Chang Y-C, Hsu Y-C, Wei P-F, Shih J-Y, Yang P-C (2008) First- or second-line therapy with gefitinib produces equal survival in non-small cell lung cancer. Am J Respir Crit Care Med 178:847–853PubMedCrossRef Wu J-Y, Yu C-J, Yang C-H, Wu S-G, Chiu Y-H, Gow C-H, Chang Y-C, Hsu Y-C, Wei P-F, Shih J-Y, Yang P-C (2008) First- or second-line therapy with gefitinib produces equal survival in non-small cell lung cancer. Am J Respir Crit Care Med 178:847–853PubMedCrossRef
23.
Zurück zum Zitat Chang GC, Tsai CM, Chen KC, Yu CJ, Shih JY, Yang TY, Lin CP, Hsu JY, Chiu CH, Perng RP, Yang PC, Yang CH (2006) Predictive factors of gefitinib antitumor activity in East Asian advanced non-small cell lung cancer patients. J Thorac Oncol 1:520–525PubMedCrossRef Chang GC, Tsai CM, Chen KC, Yu CJ, Shih JY, Yang TY, Lin CP, Hsu JY, Chiu CH, Perng RP, Yang PC, Yang CH (2006) Predictive factors of gefitinib antitumor activity in East Asian advanced non-small cell lung cancer patients. J Thorac Oncol 1:520–525PubMedCrossRef
24.
Zurück zum Zitat Murphy M, Stordal B (2011) Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resist Updat 14:177–190PubMedCrossRef Murphy M, Stordal B (2011) Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resist Updat 14:177–190PubMedCrossRef
25.
Zurück zum Zitat Yang JC, Hirsh V, Schuler M, Yamamoto N, O’Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV (2013) Symptom control and quality of life in LUX-lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3342–3350PubMedCrossRef Yang JC, Hirsh V, Schuler M, Yamamoto N, O’Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV (2013) Symptom control and quality of life in LUX-lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3342–3350PubMedCrossRef
26.
Zurück zum Zitat Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu Y-L, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP (2009) Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. The Lancet 374:1432–1440CrossRef Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu Y-L, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP (2009) Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. The Lancet 374:1432–1440CrossRef
27.
Zurück zum Zitat Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2013) PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31:2895–2902PubMedCrossRef Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2013) PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31:2895–2902PubMedCrossRef
28.
Zurück zum Zitat Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N (2013) LUX-lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol 31:3335–3341PubMedCrossRef Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N (2013) LUX-lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol 31:3335–3341PubMedCrossRef
29.
Zurück zum Zitat Fei SJ, Zhang XC, Dong S, Cheng H, Zhang YF, Huang L, Zhou HY, Xie Z, Chen ZH, Wu YL (2013) Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer cells. PLoS One 8:e69104PubMedCentralPubMedCrossRef Fei SJ, Zhang XC, Dong S, Cheng H, Zhang YF, Huang L, Zhou HY, Xie Z, Chen ZH, Wu YL (2013) Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer cells. PLoS One 8:e69104PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Xu L, Kikuchi E, Xu C, Ebi H, Ercan D, Cheng KA, Padera R, Engelman JA, Janne PA, Shapiro GI, Shimamura T, Wong KK (2012) Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutant EGFR containing T790M and MET. Cancer Res 72:3302–3311PubMedCentralPubMedCrossRef Xu L, Kikuchi E, Xu C, Ebi H, Ercan D, Cheng KA, Padera R, Engelman JA, Janne PA, Shapiro GI, Shimamura T, Wong KK (2012) Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutant EGFR containing T790M and MET. Cancer Res 72:3302–3311PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Ono N, Yamazaki T, Tsukaguchi T, Fujii T, Sakata K, Suda A, Tsukuda T, Mio T, Ishii N, Kondoh O, Aoki Y (2013) Enhanced antitumor activity of erlotinib in combination with the Hsp90 inhibitor CH5164840 against non-small cell lung cancer. Cancer Sci 104:1346–1352PubMedCrossRef Ono N, Yamazaki T, Tsukaguchi T, Fujii T, Sakata K, Suda A, Tsukuda T, Mio T, Ishii N, Kondoh O, Aoki Y (2013) Enhanced antitumor activity of erlotinib in combination with the Hsp90 inhibitor CH5164840 against non-small cell lung cancer. Cancer Sci 104:1346–1352PubMedCrossRef
32.
Zurück zum Zitat Yokouchi H, Yamazaki K, Kinoshita I, Konishi J, Asahina H, Sukoh N, Harada M, Akie K, Ogura S, Ishida T, Munakata M, Dosaka-Akita H, Isobe H, Nishimura M (2007) Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer. BMC Cancer 7:51PubMedCentralPubMedCrossRef Yokouchi H, Yamazaki K, Kinoshita I, Konishi J, Asahina H, Sukoh N, Harada M, Akie K, Ogura S, Ishida T, Munakata M, Dosaka-Akita H, Isobe H, Nishimura M (2007) Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer. BMC Cancer 7:51PubMedCentralPubMedCrossRef
33.
Zurück zum Zitat Tomizawa Y, Fujita Y, Tamura A, Shirai M, Shibata S, Kawabata T, Shibayama T, Fukai S, Kawahra M, Saito R (2010) Effect of gefitinib re-challenge to initial gefitinib responder with non-small cell lung cancer followed by chemotherapy. Lung Cancer 68:269–272PubMedCrossRef Tomizawa Y, Fujita Y, Tamura A, Shirai M, Shibata S, Kawabata T, Shibayama T, Fukai S, Kawahra M, Saito R (2010) Effect of gefitinib re-challenge to initial gefitinib responder with non-small cell lung cancer followed by chemotherapy. Lung Cancer 68:269–272PubMedCrossRef
34.
Zurück zum Zitat Beau-Faller M, Prim N, Ruppert A-M, Nanni-Metéllus I, Lacave R, Lacroix L, Escande F, Lizard S, Pretet J-L, Rouquette I, de Crémoux P, Solassol J, de Fraipont F, Bièche I, Cayre A, Favre-Guillevin E, Tomasini P, Wislez M, Besse B, Legrain M, Voegeli A-C, Baudrin L, Morin F, Zalcman G, Quoix E, Blons H, Cadranel J (2014) Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol 25:126–131PubMedCrossRef Beau-Faller M, Prim N, Ruppert A-M, Nanni-Metéllus I, Lacave R, Lacroix L, Escande F, Lizard S, Pretet J-L, Rouquette I, de Crémoux P, Solassol J, de Fraipont F, Bièche I, Cayre A, Favre-Guillevin E, Tomasini P, Wislez M, Besse B, Legrain M, Voegeli A-C, Baudrin L, Morin F, Zalcman G, Quoix E, Blons H, Cadranel J (2014) Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol 25:126–131PubMedCrossRef
35.
Zurück zum Zitat Sequist LV, Yang JC-H, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai C-M, Boyer M, Su W-C, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3327–3334PubMedCrossRef Sequist LV, Yang JC-H, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai C-M, Boyer M, Su W-C, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3327–3334PubMedCrossRef
Metadaten
Titel
EGFR–TKI is effective regardless of treatment timing in pulmonary adenocarcinoma with EGFR mutation
verfasst von
Dong-Hoe Koo
Kyu-pyo Kim
Chang-Min Choi
Dae-Ho Lee
Jae Cheol Lee
Jung-Shin Lee
Se Jin Jang
Sang-We Kim
Publikationsdatum
01.01.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 1/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2631-5

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