Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 6/2018

01-12-2018 | Original Article

A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation: Okayama Lung Cancer Study Group trial 1403

Authors: Naohiro Oda, Kastuyuki Hotta, Kiichiro Ninomiya, Daisuke Minami, Eiki Ichihara, Toshi Murakami, Toshihide Yokoyama, Hirohisa Ichikawa, Kenichi Chikamori, Nagio Takigawa, Nobuaki Ochi, Shingo Harita, Yoshinobu Maeda, Katsuyuki Kiura

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2018

Login to get access

Abstract

Purpose

The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs.

Methods

Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively.

Results

Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17% and 84%, respectively. The median PFS time was 4.2 months (95% confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%), without any treatment-related deaths.

Conclusion

EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.
Literature
1.
go back to reference 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 Group (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, randomized phase 3 trial. Lancet Oncol 11:121–128CrossRef 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 Group (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, randomized phase 3 trial. Lancet Oncol 11:121–128CrossRef
2.
go back to reference 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
3.
go back to reference 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
4.
go back to reference 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
5.
go back to reference 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
6.
go back to reference 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
7.
go back to reference 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
8.
go back to reference 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
9.
go back to reference Hotta K, Matsuo K (2007) Long-standing debate on cisplatin- versus carboplatin-based chemotherapy in the treatment of advanced non-small-cell lung cancer. J Thorac Oncol 2:96CrossRef Hotta K, Matsuo K (2007) Long-standing debate on cisplatin- versus carboplatin-based chemotherapy in the treatment of advanced non-small-cell lung cancer. J Thorac Oncol 2:96CrossRef
10.
go back to reference 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
11.
go back to reference 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
12.
go back to reference 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
13.
go back to reference 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
14.
go back to reference Hotta K, Ninomiya K, Takigawa N, Tanimoto M, Kiura K (2015) Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy; hoping for it as a public domain. Jpn J Clin Oncol 45:603–604PubMed Hotta K, Ninomiya K, Takigawa N, Tanimoto M, Kiura K (2015) Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy; hoping for it as a public domain. Jpn J Clin Oncol 45:603–604PubMed
15.
go back to reference Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J Clin Oncol 31:1070–1080CrossRef Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J Clin Oncol 31:1070–1080CrossRef
16.
go back to reference 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
18.
go back to reference 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
19.
go back to reference 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
20.
go back to reference 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 77:121–127CrossRef 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 77:121–127CrossRef
21.
go back to reference 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
22.
go back to reference 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
23.
go back to reference 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
24.
go back to reference 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
25.
go back to reference 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
26.
go back to reference 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
27.
go back to reference 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
28.
go back to reference 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
29.
go back to reference 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
30.
go back to reference 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
31.
go back to reference 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
32.
go back to reference 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
Metadata
Title
A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation: Okayama Lung Cancer Study Group trial 1403
Authors
Naohiro Oda
Kastuyuki Hotta
Kiichiro Ninomiya
Daisuke Minami
Eiki Ichihara
Toshi Murakami
Toshihide Yokoyama
Hirohisa Ichikawa
Kenichi Chikamori
Nagio Takigawa
Nobuaki Ochi
Shingo Harita
Yoshinobu Maeda
Katsuyuki Kiura
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3694-5

Other articles of this Issue 6/2018

Cancer Chemotherapy and Pharmacology 6/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine