Pharmacokinetic and dose-finding study of osimertinib in patients with impaired renal function and low body weight

Yutaka Fujiwara, Reiko Makihara, Tetsunari Hase, Naozumi Hashimoto, Tomoyuki Naito, Yukari Tsubata, Takae Okuno, Toshiaki Takahashi, Haruki Kobayashi, Yuki Shinno, Yoshitaka Zenke, Takaya Ikeda, Yukio Hosomi, Kageaki Watanabe, Satoru Kitazono, Naomi Sakiyama, Yoshinori Makino, Noboru Yamamoto

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non–small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30-50 mL/min/1.73 m2); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.

Original languageEnglish
Pages (from-to)2087-2097
Number of pages11
JournalCancer science
Volume114
Issue number5
DOIs
Publication statusPublished - 05-2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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