Osimertinib in a patient with non-small cell lung cancer and renal failure undergoing hemodialysis: a case report

  • Atsushi Matsunashi
  • Daichi FujimotoEmail author
  • Kazutaka Hosoya
  • Kei Irie
  • Shoji Fukushima
  • Keisuke Tomii


Osimertinib is a key drug for cancer patients with EGFR mutations. However, there is little information about its safety in cancer patients who require hemodialysis (HD) for chronic renal failure, despite notable increases in their numbers. Herein, we examined osimertinib safety in such a patient via pharmacokinetics analysis. A 66-year-old man was diagnosed with relapsed stage IV non-small cell lung cancer with an EGFR mutation in exon 21 (L858R) 2 years after stereotactic body radiotherapy. He was undergoing HD three times a week owing to worsening diabetic nephropathy. We administered osimertinib (80 mg/day) as the first-line therapy. We measured osimertinib concentrations on multiple days, either before, after, or in the absence of HD. Maximum concentrations and areas under the curve were determined. We found that HD did not affect the pharmacokinetics of osimertinib. We conclude that osimertinib can be safely administered to cancer patients undergoing HD.


Non-small cell lung cancer EGFR Osimertinib Hemodialysis 



The authors thank Keiko Sakuragawa for administrative assistance.

Author’s contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Atsushi Matsunashi, Daichi Fujimoto, Kazutaka Hosoya and Kei Irie. The first draft of the manuscript was written by Atsushi Matsunashi, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

Dr. Fujimoto and Dr. Hosoya received lecture fees from AstraZeneca. All the remaining authors have declared no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from the patient.


  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. CrossRefGoogle Scholar
  2. 2.
    Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380. CrossRefGoogle Scholar
  3. 3.
    Dearden S, Stevens J, Wu YL, Blowers D (2013) Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol 24(9):2371–2376. CrossRefGoogle Scholar
  4. 4.
    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 (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. CrossRefGoogle Scholar
  5. 5.
    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. CrossRefGoogle Scholar
  6. 6.
    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. CrossRefGoogle Scholar
  7. 7.
    Cengiz K (2002) Increased incidence of neoplasia in chronic renal failure (20-year experience). Int Urol Nephrol 33(1):121–126CrossRefGoogle Scholar
  8. 8.
    Luo J, Ni L, Wang M, Zhong W, Xiao Y, Zheng K, Hu P (2016) Pharmacokinetic analysis of gefitinib in a patient with advanced non-small cell lung cancer undergoing hemodialysis. Thorac Cancer 7(2):251–253. CrossRefGoogle Scholar
  9. 9.
    Shinagawa N, Yamazaki K, Asahina H, Agata J, Itoh T, Nishimura M (2007) Gefitinib administration in a patient with lung cancer undergoing hemodialysis. Lung Cancer 58(3):422–424. CrossRefGoogle Scholar
  10. 10.
    Togashi Y, Masago K, Fukudo M, Terada T, Ikemi Y, Kim YH, Fujita S, Irisa K, Sakamori Y, Mio T, Inui K, Mishima M (2010) Pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small cell lung cancer and chronic renal failure who are undergoing hemodialysis. J Thorac Oncol 5(5):601–605. CrossRefGoogle Scholar
  11. 11.
    AstraZeneca Pharmaceuticals LP (2017) TAGRISSO (osimertinib) tablets, for oral use: US prescribing information. Accessed 26 June 2019
  12. 12.
    European medicines agency Committee for Medical Products for Human Use (CHMP) Assessment report: TAGRISSO (2015) Accessed 26 June 2019
  13. 13.
    Tamura T, Takagi Y, Okubo H, Yamaguchi S, Kikkawa Y, Hashimoto I, Kaburagi T, Miura M, Satoh H, Hizawa N (2017) Plasma concentration of osimertinib in a non-small cell lung cancer patient with chronic renal failure undergoing hemodialysis. Lung Cancer 112:225–226. CrossRefGoogle Scholar
  14. 14.
    Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T (2016) Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. The Lancet Oncology 17(12):1643–1652. CrossRefGoogle Scholar
  15. 15.
    Mac-Kay MV, Fernandez IP, Herrera Carranza J, Sancez Burson J (1995) An in vitro study of the influence of a drug’s molecular weight on its overall (Clt), diffusive (Cld) and convective (Clc) clearance through dialysers. Biopharm Drug Dispos 16(1):23–35CrossRefGoogle Scholar
  16. 16.
    Watanabe Y, Yamagata K, Nishi S, Hirakata H, Hanafusa N, Saito C, Hattori M, Itami N, Komatsu Y, Kawaguchi Y, Tsuruya K, Tsubakihara Y, Suzuki K, Sakai K, Kawanishi H, Inaguma D, Yamamoto H, Takemoto Y, Mori N, Okada K, Hataya H, Akiba T, Iseki K, Tomo T, Masakane I, Akizawa T, Minakuchi J (2015) Japanese society for dialysis therapy clinical guideline for “hemodialysis initiation for maintenance hemodialysis”. Ther Apher Dial 19(Suppl 1):93–107. CrossRefGoogle Scholar
  17. 17.
    Keller F, Wilms H, Schultze G, Offerman G, Molzahn M (1983) Effect of plasma protein binding, volume of distribution and molecular weight on the fraction of drugs eliminated by hemodialysis. Clin Nephrol 19(4):201–205Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Respiratory MedicineKobe City Medical Center General HospitalKobeJapan
  2. 2.Department of PharmacyKobe City Medical Center General HospitalKobeJapan
  3. 3.Department of Pharmaceutics, Faculty of Pharmaceutical ScienceKobe Gakuin UniversityKobeJapan

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