Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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 11:121–128

    Article  CAS  Google Scholar 

  2. 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 362:2380–2388

    Article  CAS  Google Scholar 

  3. 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 13:239–246

    Article  CAS  Google Scholar 

  4. 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 12:735–742

    Article  CAS  Google Scholar 

  5. 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 31:3327–3334

    Article  CAS  Google Scholar 

  6. 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 15:213–222

    Article  CAS  Google Scholar 

  7. 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 22:3852–3859

    Article  CAS  Google Scholar 

  8. 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 15:1782–1789

    Article  CAS  Google Scholar 

  9. 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 2:96

    Article  Google Scholar 

  10. 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 109:939–948

    Article  CAS  Google Scholar 

  11. 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 43:1115–1123

    Article  Google Scholar 

  12. 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 21:81–87

    Article  CAS  Google Scholar 

  13. 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 2:632–637

    Article  Google Scholar 

  14. 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 45:603–604

    PubMed  Google Scholar 

  15. Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J Clin Oncol 31:1070–1080

    Article  CAS  Google Scholar 

  16. 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 376:629–640

    Article  CAS  Google Scholar 

  17. National Comprehensive Cancer Network (2017) NCCN clinical practice guidelines in oncology: non-small cell lung cancer. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 31 Dec 2017

  18. 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 79:423–429

    Article  CAS  Google Scholar 

  19. 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 13:458–463

    Article  CAS  Google Scholar 

  20. 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 77:121–127

    Article  Google Scholar 

  21. 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 27:4702–4711

    Article  CAS  Google Scholar 

  22. 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 31:3335–3341

    Article  CAS  Google Scholar 

  23. 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 68:269–272

    Article  Google Scholar 

  24. 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 74:268–273

    Article  Google Scholar 

  25. 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 3:90ra59

    Article  CAS  Google Scholar 

  26. 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 18:241–244

    Article  CAS  Google Scholar 

  27. 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 13:528–538

    Article  CAS  Google Scholar 

  28. 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 17:1616–1622

    Article  CAS  Google Scholar 

  29. 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 119:4325–4332

    Article  CAS  Google Scholar 

  30. 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 378:113–125

    Article  Google Scholar 

  31. 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 106:1202–1211

    Article  CAS  Google Scholar 

  32. 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 27:2103–2110

    Article  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge and thank the coordinators and all the other investigators who contributed to this study; independent data-monitoring committee members (Mikio Kataoka and Masafumi Fujii) and site investigators (Hiroshige Yoshioka [Kurashiki Central Hospital], Masayuki Yasugi [Chugoku Central Hospital], Daijiro Harada [Shikoku Cancer Center], Shoichi Kuyama, Kenichiro Kudo [Iwakuni Medical Center], Koji Inoue, Tomonori Moritaka [Ehime Prefectural Central Hospital], Masaaki Inoue [Shimonoseki City Hospital], Takuo Shibayama [Okayama Medical Center], Daizo Kishino, Etsuko Kurimoto [Himeji Red Cross Hospital], and Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Go Makimoto, Satoru Senoo, Kazuya Nishii, Hiromi Watanabe, Chihiro Ando, Masahiro Tabata, Taizo Hirata, Hisao Higo [Okayama University Hospital]). The study received support from the Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. The study received no specific grant from any profit fundings.

Author information

Authors and Affiliations

  1. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan

    Naohiro Oda, Kastuyuki Hotta, Kiichiro Ninomiya, Eiki Ichihara & Katsuyuki Kiura

  2. Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho Kita-ku, Okayama, Okayama, 700-8558, Japan

    Kastuyuki Hotta

  3. Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan

    Daisuke Minami

  4. Department of Respiratory Medicine, Himeji Red Cross Hospital, Himeji, Japan

    Toshi Murakami

  5. Department of Respiratory Medicine, Onomichi City Hospital, Onomichi, Japan

    Toshi Murakami

  6. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan

    Toshihide Yokoyama

  7. Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, Japan

    Hirohisa Ichikawa

  8. Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan

    Kenichi Chikamori

  9. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan

    Nagio Takigawa & Nobuaki Ochi

  10. Department of Respiratory Medicine, Okayama Saiseikai General Hospital, Okayama, Japan

    Shingo Harita

  11. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan

    Shingo Harita

  12. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    Yoshinobu Maeda

Authors
  1. Naohiro Oda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kastuyuki Hotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiichiro Ninomiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daisuke Minami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eiki Ichihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshi Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshihide Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hirohisa Ichikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kenichi Chikamori
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nagio Takigawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nobuaki Ochi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shingo Harita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yoshinobu Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Katsuyuki Kiura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kastuyuki Hotta.

Ethics declarations

Conflict of interest

NO has received grants from Boehringer-Ingelheim, during the conduct of the study. KH has received grants and personal fees from Boehringer-Ingelheim, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from Ono Pharmaceutical, personal fees from Nihon Kayaku, personal fees from Taiho Pharmaceutical, grants and personal fees from Chugai Pharmaceutical, personal fees from Astellas, grants and personal fees from Novartis, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Eli Lilly Japan, grants and personal fees from Merck Sharp Dohme, outside the submitted work. KN has received grants from Boehringer-Ingelheim, during the conduct of the study; personal fees from Bristol-Myers Squibb, other from AstraZeneca, personal fees from Ono Pharmaceutical, outside the submitted work. EI has received grants from Boehringer-Ingelheim, during the conduct of the study; personal fees from AstraZeneca, personal fees from Ono Pharmaceutical, grants and personal fees from Merck Sharp Dohme, personal fees from Chugai Pharmaceutical, personal fees from Novartis, personal fees from Bristol-Myers Squibb, grants from Eli Lilly Japan, outside the submitted work. TY has received personal fees from AstraZeneca, personal fees from Ono Pharmaceutical, personal fees from Taiho Pharmaceutical, personal fees from Eli Lilly Japan, outside the submitted work. KC has received grants and personal fees from Chugai pharmaceutical, grants from Bristol-Myers Squibb, personal fees from Eli Lilly Japan, grants from Taiho Pharmaceutical, personal fees from Ono Pharmaceutical, outside the submitted work;. NT has received grants and personal fees from Eli Lilly Japan, grants and personal fees from AstraZeneca, grants and personal fees from Daiichi-Sankyo Pharmaceutical, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Pfizer Inc. Japan, grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Ono Pharmaceutical, grants and personal fees from Kyowa Hakko Kirin, grants from Nippon Kayaku, grants from Takeda Pharmaceutical, personal fees from Merck Sharp Dohme, personal fees from Novartis, outside the submitted work. YM has received grants from Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceutical, Kyowa Hakko Kirin, Merck Sharp Dohme, Eisai, Mochida Pharmaceutical, Ono Pharmaceutical, Astellas, Meiji Seika Pharma, Asahi Kasei Pharma., Nippon Shinyaku, Toyama Chemical., and Yakult Honsha, outside the submitted work. KK has received from personal fees from Nippon Boehringer-Ingelheim, during the conduct of the study; grants from Chugai Pharmaceutical, grants from Pfizer, grants from Novartis, grants and personal fees from Taiho pharmaceutical, grants from Eli Lilly Japan, grants and personal fees from Ono Pharmaceutical, personal fees from AstraZeneca, personal fees from Nippon Kayaku, personal fees from Daiichi Sankyo, personal fees from Shionogi, outside the submitted work. All other authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oda, N., Hotta, K., Ninomiya, K. et al. 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. Cancer Chemother Pharmacol 82, 1031–1038 (2018). https://doi.org/10.1007/s00280-018-3694-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-018-3694-5

Keywords

Search

Navigation