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Retrospective analysis of osimertinib re-challenge after osimertinib-induced interstitial lung disease in patients with EGFR-mutant non-small cell lung carcinoma

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Summary

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has exhibited efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a fatal adverse event of osimertinib treatment, and it requires treatment discontinuation. There are few reports regarding the safety and efficacy of osimertinib re-challenge in patients who experienced osimertinib-induced ILD. This retrospective study assessed this treatment option. We retrospectively collected data for patients treated with osimertinib who developed ILD at Shizuoka Cancer Center from April 2016 to March 2020. ILD was diagnosed by two doctors based on imaging tests and blood tests to exclude other causes. Among 215 patients treated with osimertinib, 28 developed ILD. The median age of patients with ILD was 69.5 years (range, 39.0–80.0). In addition, 29% of patients were men, and 46% had a history of smoking. Eleven patients were re-administered EGFR TKIs, including eight patients treated with osimertinib and three patients treated with alternative EGFR TKIs. Among patients re-challenged with osimertinib, none who previously experienced grade 1 ILD exhibited ILD relapse, even with the same osimertinib dose and without the concurrent administration of systemic steroids. Meanwhile, one of the four patients who previously exhibited grade 2 ILD experienced despite a dose reduction for osimertinib and systemic steroid administration. For patients with EGFR-mutant NSCLC who experience grade 1 ILD during osimertinib therapy, osimertinib re-challenge may be suitable when no other treatments are available.

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References

  1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, Znaor A, Bray F (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 144(8):1941–1953. https://doi.org/10.1002/ijc.31937

    Article  CAS  PubMed  Google Scholar 

  2. Lee CK, Davies L, Wu YL, Mitsudomi T, Inoue A, Rosell R, Zhou C, Nakagawa K, Thongprasert S, Fukuoka M, Lord S, Marschner I, Tu YK, Gralla RJ, Gebski V, Mok T, Yang JC (2017) Gefitinib or Erlotinib vs chemotherapy for EGFR mutation-positive lung Cancer: individual patient data meta-analysis of overall survival. J Natl Cancer Inst 109(6). https://doi.org/10.1093/jnci/djw279

  3. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388. https://doi.org/10.1056/NEJMoa0909530

    Article  CAS  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. 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 (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

    Article  CAS  PubMed  Google Scholar 

  6. Mok TS, Wu YL, Ahn MJ, 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) Osimertinib or platinum-Pemetrexed in EGFR T790M-positive lung Cancer. N Engl J Med 376(7):629–640. https://doi.org/10.1056/NEJMoa1612674

    Article  CAS  PubMed  Google Scholar 

  7. Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne PA, Mann H, Cantarini M, Goss G (2019) Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer 125(6):892–901. https://doi.org/10.1002/cncr.31891

    Article  CAS  PubMed  Google Scholar 

  8. Noonan SA, Sachs PB, Camidge DR (2016) Transient asymptomatic pulmonary opacities occurring during Osimertinib treatment. J Thorac Oncol 11(12):2253–2258. https://doi.org/10.1016/j.jtho.2016.08.144

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kobayashi K, Naoki K, Kuroda A, Yasuda H, Kawada I, Soejima K, Betsuyaku T (2018) EGFR-mutant non-small cell lung Cancer accompanied by transient asymptomatic pulmonary opacities successfully treated with "stop-and-go" Osimertinib. Intern Med 57(7):1007–1010. https://doi.org/10.2169/internalmedicine.9609-17

    Article  PubMed  Google Scholar 

  10. Satoh S, Shiroyama T, Tamiya M, Nasu S, Tanaka A, Morita S, Morishita N, Suzuki H, Okamoto N, Hirashima T (2018) Successful osimertinib rechallenge after osimertinib-induced pneumonitis in a patient with lung adenocarcinoma. Respir Med Case Rep 23:68–70. https://doi.org/10.1016/j.rmcr.2017.12.005

    Article  PubMed  Google Scholar 

  11. Kiriu T, Tamura D, Tachihara M, Sekiya R, Hazama D, Katsurada M, Nakata K, Nagano T, Yamamoto M, Kamiryo H, Kobayashi K, Nishimura Y (2018) Successful Osimertinib Rechallenge with steroid therapy after Osimertinib-induced interstitial lung disease. Intern Med 57(1):91–95. https://doi.org/10.2169/internalmedicine.8947-17

    Article  PubMed  Google Scholar 

  12. Itano J, Higo H, Ohashi K, Makimoto G, Nishii K, Hotta K, Miyahara N, Maeda Y, Kiura K (2020) Successful re-administration of Osimertinib in Osimertinib-induced interstitial lung disease with an organizing pneumonia pattern: a case report and literature review. Intern Med 59(6):823–828. https://doi.org/10.2169/internalmedicine.3689-19

    Article  PubMed  Google Scholar 

  13. Matsuo T, Imai K, Takashima S, Atari M, Watanabe S-n, Minamiya Y (2019) Successful Osimertinib Rechallenge after Osimertinib-induced interstitial lung disease in a patient with postoperative recurrence of lung Cancer. Haigan 59(7):1184–1189. https://doi.org/10.2482/haigan.59.1184

    Article  Google Scholar 

  14. Nagasaka M, Gadgeel SM (2018) Retreatment with Osimertinib following pneumonitis. Clin Lung Cancer 19(1):e53–e55. https://doi.org/10.1016/j.cllc.2017.06.017

    Article  PubMed  Google Scholar 

  15. Merad M, Le Cesne A, Baldeyrou P, Mesurolle B, Le Chevalier T (1997) Docetaxel and interstitial pulmonary injury. Ann Oncol 8 (2):191-194. https://doi.org/10.1023/a:1008226416896

  16. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  17. Ohe Y, Imamura F, Nogami N, Okamoto I, Kurata T, Kato T, Sugawara S, Ramalingam SS, Uchida H, Hodge R, Vowler SL, Walding A, Nakagawa K (2019) Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset. Jpn J Clin Oncol 49(1):29–36. https://doi.org/10.1093/jjco/hyy179

    Article  PubMed  Google Scholar 

  18. Lee H, Lee HY, Sun JM, Lee SH, Kim Y, Park SE, Ahn JS, Park K, Ahn MJ (2018) Transient asymptomatic pulmonary opacities during Osimertinib treatment and its clinical implication. J Thorac Oncol 13(8):1106–1112. https://doi.org/10.1016/j.jtho.2018.04.038

    Article  CAS  PubMed  Google Scholar 

  19. Miyauchi E, Ichinose M, Inoue A (2017) Successful Osimertinib Rechallenge in a patient with T790M-mutant non-small cell lung Cancer after Osimertinib-induced interstitial lung disease. J Thorac Oncol 12(5):e59–e61. https://doi.org/10.1016/j.jtho.2017.01.027

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Joe Barber Jr., PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho Suntou-gun, Shizuoka, 411-8777, Japan

    Hiroaki Kodama, Kazushige Wakuda, Michitoshi Yabe, Naoya Nishioka, Eriko Miyawaki, Taichi Miyawaki, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Shota Omori, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami & Toshiaki Takahashi

  2. Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho Suntou-gun, Shizuoka, 411-8777, Japan

    Masahiro Endo

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  1. Hiroaki Kodama
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Hiroaki Kodama, Kazushige Wakuda, and Masahiro Endo. The first draft of the manuscript was written by Hiroaki Kodama, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kazushige Wakuda.

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Conflict of interest

K. Wakuda reports grants and personal fees from AstraZeneca and Chugai Pharmaceutical Co., Ltd.; personal fees from Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly K.K., Ono Pharmaceutical, and MSD; and grants from Novartis and AbbVie, all outside the submitted work. S. Omori reports grants from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical, AstraZeneca K.K., Boehringer Ingelheim, Taiho Pharmaceutical, and MSD K.K., all outside the submitted work. H. Kobayashi reports grants from Eli Lilly K.K and Taiho Pharmaceutical, both outside the submitted work. A. Ono reports grants from Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharmaceutical Co., Ltd., and Novartis Pharma K.K., all outside the submitted work. H. Kenmotsu reports grants and personal fees from AstraZeneca KK, Pfizer Japan, Inc., Chugai Pharmaceutical Co., Ltd., and Boehringer Ingelheim and grants from Kyowa Hakko Kirin Co., Ltd., Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Pfizer K.K., Eli Lilly K.K, Bristol-Myers Squibb, Ono Pharmaceutical Co, Ltd., and MSD K.K., all outside the submitted work. T. Naito reports grants from Ono Pharmaceutical Co., Ltd., Pfizer US, Inc., and Mochida Pharmaceutical Co., Ltd., all outside the submitted work. H. Murakami reports grants and personal fees from AstraZeneca KK, Pfizer Japan, Inc., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical; grants from AbbVie, Daiichi Sankyo, and IQvia; and personal fees from Bristol-Myers Squibb Japan, Ono Pharmaceutical, and MSD K.K., all outside the submitted work. M. Endo reports personal fees from AstraZeneca Co., outside the submitted work. T. Takahashi reports grants and personal fees from AstraZeneca KK, Pfizer Japan, Inc., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan, Inc., and Pfizer Japan, Inc. and personal fees from Roche Diagnostics K.K., all outside the submitted work. The remaining authors have not conflicts of interest to declare.

Ethics approval

All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the Clinical Research Ethics Committee of Shizuoka Cancer Center Hospital and Research Institute.

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The ethics review board of Shizuoka Cancer Center approved the present study and permitted the use of the opt-out method in lieu of written informed consent.

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Kodama, H., Wakuda, K., Yabe, M. et al. Retrospective analysis of osimertinib re-challenge after osimertinib-induced interstitial lung disease in patients with EGFR-mutant non-small cell lung carcinoma. Invest New Drugs 39, 571–577 (2021). https://doi.org/10.1007/s10637-020-01005-1

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