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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 Group (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388CrossRef 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 Group (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388CrossRef

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, Muñoz-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) Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. 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, randomized phase 3 trial. Lancet Oncol 13:239–246CrossRef 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, Muñoz-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) Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. 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, randomized phase 3 trial. Lancet Oncol 13:239–246CrossRef

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 (2012) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicenter, open label, randomized, phase 3 study. Lancet Oncol 12:735–742CrossRef 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 (2012) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicenter, open label, randomized, phase 3 study. Lancet Oncol 12:735–742CrossRef

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 31:3327–3334CrossRef 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 31:3327–3334CrossRef

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 15:213–222CrossRef 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 15:213–222CrossRef

Zurück zum Zitat Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004) Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22:3852–3859CrossRef Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004) Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22:3852–3859CrossRef

Zurück zum Zitat Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004) Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials. Ann Oncol 15:1782–1789CrossRef Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004) Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials. Ann Oncol 15:1782–1789CrossRef

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Zurück zum Zitat Hotta K, Fujiwara Y, Matsuo K, Suzuki T, Kiura K, Tabata M, Takigawa N, Ueoka H, Tanimoto M (2007) Recent improvement in the survival of patients with advanced non small cell lung cancer enrolled in phase III trials of first-line, systemic chemotherapy. Cancer 109:939–948CrossRef Hotta K, Fujiwara Y, Matsuo K, Suzuki T, Kiura K, Tabata M, Takigawa N, Ueoka H, Tanimoto M (2007) Recent improvement in the survival of patients with advanced non small cell lung cancer enrolled in phase III trials of first-line, systemic chemotherapy. Cancer 109:939–948CrossRef

Zurück zum Zitat Hotta K, Takigawa N, Hisamoto-Sato A, Ichihara E, Kudo K, Uchida K, Yanase-Nakamura K, Tanaka H, Kato Y, Tabata M, Tanimoto M, Kiura K (2013) Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy: results of a prospective feasibility study in advanced lung cancer in the Okayama Lung Cancer Study Group Trial 1002. Jpn J Clin Oncol 43:1115–1123CrossRef Hotta K, Takigawa N, Hisamoto-Sato A, Ichihara E, Kudo K, Uchida K, Yanase-Nakamura K, Tanaka H, Kato Y, Tabata M, Tanimoto M, Kiura K (2013) Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy: results of a prospective feasibility study in advanced lung cancer in the Okayama Lung Cancer Study Group Trial 1002. Jpn J Clin Oncol 43:1115–1123CrossRef

Zurück zum Zitat Ninomiya K, Hotta K, Hisamoto-Sato A, Ichihara E, Gotoda H, Morichika D, Tamura T, Kayatani H, Minami D, Kubo T, Tabata M, Tanimoto M, Kiura K (2016) Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201. Int J Clin Oncol 21:81–87CrossRef Ninomiya K, Hotta K, Hisamoto-Sato A, Ichihara E, Gotoda H, Morichika D, Tamura T, Kayatani H, Minami D, Kubo T, Tabata M, Tanimoto M, Kiura K (2016) Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201. Int J Clin Oncol 21:81–87CrossRef

Zurück zum Zitat Hotta K, Kiura K, Toyooka S, Takigawa N, Soh J, Fujiwara Y, Tabata M, Date H, Tanimoto M (2007) Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small-cell lung cancer. J Thorac Oncol 2:632–637CrossRef Hotta K, Kiura K, Toyooka S, Takigawa N, Soh J, Fujiwara Y, Tabata M, Date H, Tanimoto M (2007) Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small-cell lung cancer. J Thorac Oncol 2:632–637CrossRef

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Zurück zum Zitat Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA (2017) AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med 376:629–640CrossRef Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA (2017) AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med 376:629–640CrossRef

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Zurück zum Zitat Asahina H, Oizumi S, Inoue A, Kinoshita I, Ishida T, Fujita Y, Sukoh N, Harada M, Maemondo M, Saijo Y, Dosaka-Akita H, Isobe H, Nukiwa T, Nishimura M, Hokkaido Lung Cancer Clinical Study Group (2010) Phase II study of gefitinib re-administration in patients with advanced non-small cell lung cancer and previous response to gefitinib. Oncology 79:423–429CrossRef Asahina H, Oizumi S, Inoue A, Kinoshita I, Ishida T, Fujita Y, Sukoh N, Harada M, Maemondo M, Saijo Y, Dosaka-Akita H, Isobe H, Nukiwa T, Nishimura M, Hokkaido Lung Cancer Clinical Study Group (2010) Phase II study of gefitinib re-administration in patients with advanced non-small cell lung cancer and previous response to gefitinib. Oncology 79:423–429CrossRef

Zurück zum Zitat Koizumi T, Agatsuma T, Ikegami K, Suzuki T, Kobayashi T, Kanda S, Yoshikawa S, Kubo K, Shiina T, Takasuna K, Matsuo A, Hayasaka M, Morikawa M, Ameshima S (2012) Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib. Clin Lung Cancer 13:458–463CrossRef Koizumi T, Agatsuma T, Ikegami K, Suzuki T, Kobayashi T, Kanda S, Yoshikawa S, Kubo K, Shiina T, Takasuna K, Matsuo A, Hayasaka M, Morikawa M, Ameshima S (2012) Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib. Clin Lung Cancer 13:458–463CrossRef

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Zurück zum Zitat Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H, Wong KK (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27:4702–4711CrossRef Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H, Wong KK (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27:4702–4711CrossRef

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 31:3335–3341CrossRef 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 31:3335–3341CrossRef

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 68:269–272CrossRef 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 68:269–272CrossRef

Zurück zum Zitat Hata A, Katakami N, Yoshioka H, Fujita S, Kunimasa K, Nanjo S, Otsuka K, Kaji R, Tomii K, Iwasaku M, Nishiyama A, Hayashi H, Morita S, Ishida T (2011) Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection. Lung Cancer 74:268–273CrossRef Hata A, Katakami N, Yoshioka H, Fujita S, Kunimasa K, Nanjo S, Otsuka K, Kaji R, Tomii K, Iwasaku M, Nishiyama A, Hayashi H, Morita S, Ishida T (2011) Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection. Lung Cancer 74:268–273CrossRef

Zurück zum Zitat Chmielecki J, Foo J, Oxnard GR, Hutchinson K, Ohashi K, Somwar R, Wang L, Amato KR, Arcila M, Sos ML, Socci ND, Viale A, de Stanchina E, Ginsberg MS, Thomas RK, Kris MG, Inoue A, Ladanyi M, Miller VA, Michor F, Pao W (2011) Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci Transl Med 3:90ra59CrossRef Chmielecki J, Foo J, Oxnard GR, Hutchinson K, Ohashi K, Somwar R, Wang L, Amato KR, Arcila M, Sos ML, Socci ND, Viale A, de Stanchina E, Ginsberg MS, Thomas RK, Kris MG, Inoue A, Ladanyi M, Miller VA, Michor F, Pao W (2011) Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci Transl Med 3:90ra59CrossRef

Zurück zum Zitat Oda N, Ichihara E, Hotta K, Ninomiya K, Ninomiya T, Kubo T, Minami D, Murakami T, Yokoyama T, Harada D, Kuyama S, Ichikawa H, Inoue K, Kishino D, Inoue M, Takigawa N, Shibayama T, Harita S, Tanimoto M, Kiura K (2017) Phase II Study of the EGFR-TKI rechallenge with afatinib in patients with advanced NSCLC harboring sensitive EGFR mutation without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403. Clin Lung Cancer 18:241–244CrossRef Oda N, Ichihara E, Hotta K, Ninomiya K, Ninomiya T, Kubo T, Minami D, Murakami T, Yokoyama T, Harada D, Kuyama S, Ichikawa H, Inoue K, Kishino D, Inoue M, Takigawa N, Shibayama T, Harita S, Tanimoto M, Kiura K (2017) Phase II Study of the EGFR-TKI rechallenge with afatinib in patients with advanced NSCLC harboring sensitive EGFR mutation without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403. Clin Lung Cancer 18:241–244CrossRef

Zurück zum Zitat Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC (2012) Afatinib versus placebo for patients with advanced, metastatic non-small cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 13:528–538CrossRef Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC (2012) Afatinib versus placebo for patients with advanced, metastatic non-small cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 13:528–538CrossRef

Zurück zum Zitat Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA (2011) 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 17:1616–1622CrossRef Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA (2011) 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 17:1616–1622CrossRef

Zurück zum Zitat Hata A, Katakami N, Yoshioka H, Takeshita J, Tanaka K, Nanjo S, Fujita S, Kaji R, Imai Y, Monden K, Matsumoto T, Nagata K, Otsuka K, Tachikawa R, Tomii K, Kunimasa K, Iwasaku M, Nishiyama A, Ishida T, Nishimura Y (2013) Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: comparison between T790M mutation-positive and mutation-negative populations. Cancer 119:4325–4332CrossRef Hata A, Katakami N, Yoshioka H, Takeshita J, Tanaka K, Nanjo S, Fujita S, Kaji R, Imai Y, Monden K, Matsumoto T, Nagata K, Otsuka K, Tachikawa R, Tomii K, Kunimasa K, Iwasaku M, Nishiyama A, Ishida T, Nishimura Y (2013) Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: comparison between T790M mutation-positive and mutation-negative populations. Cancer 119:4325–4332CrossRef

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, FLAURA Investigators. (2018) Osimertinib in Untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378:113–125CrossRef 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, FLAURA Investigators. (2018) Osimertinib in Untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378:113–125CrossRef

Zurück zum Zitat Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N (2015) Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: subgroup analysis of LUX-Lung 3. Cancer Sci 106:1202–1211CrossRef Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N (2015) Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: subgroup analysis of LUX-Lung 3. Cancer Sci 106:1202–1211CrossRef

Zurück zum Zitat Yang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O’Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL (2016) Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol 27:2103–2110CrossRef Yang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O’Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL (2016) Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol 27:2103–2110CrossRef