A phase II trial of induction of erlotinib followed by cytotoxic chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer patients

Zurück zum Zitat Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29. https://doi.org/10.3322/caac.21254 CrossRefPubMed Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29. https://​doi.​org/​10.​3322/​caac.​21254 CrossRefPubMed

Zurück zum Zitat 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):1497–1500. https://doi.org/10.1126/science.1099314 CrossRefPubMed 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):1497–1500. https://​doi.​org/​10.​1126/​science.​1099314 CrossRefPubMed

Zurück zum Zitat Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566. https://doi.org/10.1038/nature05945 CrossRefPubMed Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566. https://​doi.​org/​10.​1038/​nature05945 CrossRefPubMed

Zurück zum Zitat Slebos RJ, Kibbelaar RE, Dalesio O, Kooistra A, Stam J, Meijer CJ, Wagenaar SS, Vanderschueren RG, van Zandwijk N, Mooi WJ et al (1990) K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 323(9):561–565. https://doi.org/10.1056/NEJM199008303230902 CrossRefPubMed Slebos RJ, Kibbelaar RE, Dalesio O, Kooistra A, Stam J, Meijer CJ, Wagenaar SS, Vanderschueren RG, van Zandwijk N, Mooi WJ et al (1990) K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 323(9):561–565. https://​doi.​org/​10.​1056/​NEJM199008303230​902 CrossRefPubMed

Zurück zum Zitat Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansen S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Janne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150(6):1107–1120. https://doi.org/10.1016/j.cell.2012.08.029 CrossRefPubMedPubMedCentral Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansen S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Janne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150(6):1107–1120. https://​doi.​org/​10.​1016/​j.​cell.​2012.​08.​029 CrossRefPubMedPubMedCentral

Zurück zum Zitat Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12(2):175–180. https://doi.org/10.1016/S1470-2045(10)70087-5 CrossRefPubMed Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12(2):175–180. https://​doi.​org/​10.​1016/​S1470-2045(10)70087-5 CrossRefPubMed

Zurück zum Zitat Pao W, Hutchinson KE (2012) Chipping away at the lung cancer genome. Nat Med 18(3):349–351. https://doi.org/10.1038/nm.2697 CrossRefPubMed Pao W, Hutchinson KE (2012) Chipping away at the lung cancer genome. Nat Med 18(3):349–351. https://​doi.​org/​10.​1038/​nm.​2697 CrossRefPubMed

Zurück zum Zitat Li T, Kung HJ, Mack PC, Gandara DR (2013) Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 31(8):1039–1049. https://doi.org/10.1200/JCO.2012.45.3753 CrossRefPubMedPubMedCentral Li T, Kung HJ, Mack PC, Gandara DR (2013) Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 31(8):1039–1049. https://​doi.​org/​10.​1200/​JCO.​2012.​45.​3753 CrossRefPubMedPubMedCentral

Zurück zum Zitat Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) 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(21):3543–3551. https://doi.org/10.1200/JCO.2007.15.0375 CrossRefPubMed Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) 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(21):3543–3551. https://​doi.​org/​10.​1200/​JCO.​2007.​15.​0375 CrossRefPubMed

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(24):2542–2550. https://doi.org/10.1056/NEJMoa061884 CrossRefPubMed 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(24):2542–2550. https://​doi.​org/​10.​1056/​NEJMoa061884 CrossRefPubMed

Zurück zum Zitat Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27(8):1227–1234. https://doi.org/10.1200/JCO.2007.14.5466 CrossRefPubMed Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27(8):1227–1234. https://​doi.​org/​10.​1200/​JCO.​2007.​14.​5466 CrossRefPubMed

Zurück zum Zitat 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):947–957. https://doi.org/10.1056/NEJMoa0810699 CrossRefPubMed 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):947–957. https://​doi.​org/​10.​1056/​NEJMoa0810699 CrossRefPubMed

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, North-East Japan Study G (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388. https://doi.org/10.1056/nejmoa0909530 CrossRefPubMed 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, North-East Japan Study G (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388. https://​doi.​org/​10.​1056/​nejmoa0909530 CrossRefPubMed

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, West Japan Oncology G (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(2):121–128. https://doi.org/10.1016/S1470-2045(09)70364-X CrossRefPubMed 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, West Japan Oncology G (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(2):121–128. https://​doi.​org/​10.​1016/​S1470-2045(09)70364-X CrossRefPubMed

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(8):735–742. https://doi.org/10.1016/S1470-2045(11)70184-X CrossRefPubMed 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(8):735–742. https://​doi.​org/​10.​1016/​S1470-2045(11)70184-X CrossRefPubMed

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, Spanish Lung Cancer Group in collaboration with Groupe Francais de P-C, Associazione Italiana Oncologia T (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(3):239–246. https://doi.org/10.1016/s1470-2045(11)70393-x CrossRefPubMed 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, Spanish Lung Cancer Group in collaboration with Groupe Francais de P-C, Associazione Italiana Oncologia T (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(3):239–246. https://​doi.​org/​10.​1016/​s1470-2045(11)70393-x CrossRefPubMed

Zurück zum Zitat Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, 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(27):3327–3334. https://doi.org/10.1200/JCO.2012.44.2806 CrossRefPubMed Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, 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(27):3327–3334. https://​doi.​org/​10.​1200/​JCO.​2012.​44.​2806 CrossRefPubMed

Zurück zum Zitat Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15(2):213–222. https://doi.org/10.1016/S1470-2045(13)70604-1 CrossRefPubMed Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15(2):213–222. https://​doi.​org/​10.​1016/​S1470-2045(13)70604-1 CrossRefPubMed

Zurück zum Zitat Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O’Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV (2015) Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16(2):141–151. https://doi.org/10.1016/S1470-2045(14)71173-8 CrossRefPubMed Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O’Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV (2015) Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16(2):141–151. https://​doi.​org/​10.​1016/​S1470-2045(14)71173-8 CrossRefPubMed

Zurück zum Zitat Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T (2013) Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol 14(8):777–786. https://doi.org/10.1016/S1470-2045(13)70254-7 CrossRefPubMed Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T (2013) Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol 14(8):777–786. https://​doi.​org/​10.​1016/​S1470-2045(13)70254-7 CrossRefPubMed

Zurück zum Zitat Sugawara S, Oizumi S, Minato K, Harada T, Inoue A, Fujita Y, Maemondo M, Yoshizawa H, Ito K, Gemma A, Nishitsuji M, Harada M, Isobe H, Kinoshita I, Morita S, Kobayashi K, Hagiwara K, Kurihara M, Nukiwa T, North East Japan Study G, Tokyo Cooperative Oncology G (2015) Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902. Ann Oncol 26(5):888–894. https://doi.org/10.1093/annonc/mdv063 CrossRefPubMed Sugawara S, Oizumi S, Minato K, Harada T, Inoue A, Fujita Y, Maemondo M, Yoshizawa H, Ito K, Gemma A, Nishitsuji M, Harada M, Isobe H, Kinoshita I, Morita S, Kobayashi K, Hagiwara K, Kurihara M, Nukiwa T, North East Japan Study G, Tokyo Cooperative Oncology G (2015) Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902. Ann Oncol 26(5):888–894. https://​doi.​org/​10.​1093/​annonc/​mdv063 CrossRefPubMed

Zurück zum Zitat Watanabe S, Tanaka J, Ota T, Kondo R, Tanaka H, Kagamu H, Ichikawa K, Koshio J, Baba J, Miyabayashi T, Narita I, Yoshizawa H (2011) Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. BMC Cancer 11:1. https://doi.org/10.1186/1471-2407-11-1 CrossRefPubMedPubMedCentral Watanabe S, Tanaka J, Ota T, Kondo R, Tanaka H, Kagamu H, Ichikawa K, Koshio J, Baba J, Miyabayashi T, Narita I, Yoshizawa H (2011) Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. BMC Cancer 11:1. https://​doi.​org/​10.​1186/​1471-2407-11-1 CrossRefPubMedPubMedCentral

Zurück zum Zitat Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N (2014) Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 15(11):1236–1244. https://doi.org/10.1016/S1470-2045(14)70381-X CrossRefPubMed Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N (2014) Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 15(11):1236–1244. https://​doi.​org/​10.​1016/​S1470-2045(14)70381-X CrossRefPubMed

Zurück zum Zitat Becker A, Crombag L, Heideman DA, Thunnissen FB, van Wijk AW, Postmus PE, Smit EF (2011) Retreatment with erlotinib: regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur J Cancer 47(17):2603–2606. https://doi.org/10.1016/j.ejca.2011.06.046 CrossRefPubMed Becker A, Crombag L, Heideman DA, Thunnissen FB, van Wijk AW, Postmus PE, Smit EF (2011) Retreatment with erlotinib: regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur J Cancer 47(17):2603–2606. https://​doi.​org/​10.​1016/​j.​ejca.​2011.​06.​046 CrossRefPubMed

Zurück zum Zitat Oh IJ, Ban HJ, Kim KS, Kim YC (2012) Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer 77(1):121–127. https://doi.org/10.1016/j.lungcan.2012.01.012 CrossRefPubMed Oh IJ, Ban HJ, Kim KS, Kim YC (2012) Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer 77(1):121–127. https://​doi.​org/​10.​1016/​j.​lungcan.​2012.​01.​012 CrossRefPubMed

Zurück zum Zitat Song Z, Yu X, He C, Zhang B, Zhang Y (2013) Re-administration after the failure of gefitinib or erlotinib in patients with advanced non-small cell lung cancer. J Thorac Dis 5(4):400–405. https://doi.org/10.3978/j.issn.2072-1439.2013.07.28 CrossRefPubMedPubMedCentral Song Z, Yu X, He C, Zhang B, Zhang Y (2013) Re-administration after the failure of gefitinib or erlotinib in patients with advanced non-small cell lung cancer. J Thorac Dis 5(4):400–405. https://​doi.​org/​10.​3978/​j.​issn.​2072-1439.​2013.​07.​28 CrossRefPubMedPubMedCentral

Zurück zum Zitat Xia GH, Zeng Y, Fang Y, Yu SR, Wang L, Shi MQ, Sun WL, Huang XE, Chen J, Feng JF (2014) Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI. Cancer Biol Med 11(4):270–276. https://doi.org/10.7497/j.issn.2095-3941.2014.04.006 CrossRefPubMedPubMedCentral Xia GH, Zeng Y, Fang Y, Yu SR, Wang L, Shi MQ, Sun WL, Huang XE, Chen J, Feng JF (2014) Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI. Cancer Biol Med 11(4):270–276. https://​doi.​org/​10.​7497/​j.​issn.​2095-3941.​2014.​04.​006 CrossRefPubMedPubMedCentral

Zurück zum Zitat Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS, Investigators FLAURA (2018) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378(2):113–125. https://doi.org/10.1056/NEJMoa1713137 CrossRefPubMed Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS, Investigators FLAURA (2018) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378(2):113–125. https://​doi.​org/​10.​1056/​NEJMoa1713137 CrossRefPubMed