Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL

Shigehiro Yagishita, MD, PhD; Yasushi Goto, MD, PhD; Makoto Nishio, MD, PhD; Hiroaki Akamatsu, MD, PhD; Hidetoshi Hayashi, MD, PhD; Satoru Miura, MD, PhD; Koji Tamada, MD, PhD; Hiroshi Kagamu, MD, PhD; Akinobu Hamada, PhD; Mayu Ohuchi, PhD; Akihiko Gemma, MD, PhD; Ichiro Yoshino, MD, PhD; Toshihiro Misumi, PhD; Akito Hata, MD; Satoshi Hara, MD; Takashi Kijima, MD, PhD; Fujita Masaki, MD, PhD; Shunichiro Iwasawa, MD, PhD; Shintaro Nakagawa, MSc; Masahiro Tatsuno, MSc; Tetsuya Mitsudomi, MD, PhD

JTO Clinical and Research Reports (Jul 2024)

Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL

Shigehiro Yagishita, MD, PhD,
Yasushi Goto, MD, PhD,
Makoto Nishio, MD, PhD,
Hiroaki Akamatsu, MD, PhD,
Hidetoshi Hayashi, MD, PhD,
Satoru Miura, MD, PhD,
Koji Tamada, MD, PhD,
Hiroshi Kagamu, MD, PhD,
Akinobu Hamada, PhD,
Mayu Ohuchi, PhD,
Akihiko Gemma, MD, PhD,
Ichiro Yoshino, MD, PhD,
Toshihiro Misumi, PhD,
Akito Hata, MD,
Satoshi Hara, MD,
Takashi Kijima, MD, PhD,
Fujita Masaki, MD, PhD,
Shunichiro Iwasawa, MD, PhD,
Shintaro Nakagawa, MSc,
Masahiro Tatsuno, MSc,
Tetsuya Mitsudomi, MD, PhD

Affiliations

Shigehiro Yagishita, MD, PhD: Division of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan
Yasushi Goto, MD, PhD: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
Makoto Nishio, MD, PhD: Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
Hiroaki Akamatsu, MD, PhD: Internal Medicine III, Wakayama Medical University, Wakayama, Japan
Hidetoshi Hayashi, MD, PhD: Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan
Satoru Miura, MD, PhD: Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan
Koji Tamada, MD, PhD: Department of Immunology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
Hiroshi Kagamu, MD, PhD: Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
Akinobu Hamada, PhD: Division of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan
Mayu Ohuchi, PhD: Department of Pharmacology and Therapeutics, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan
Akihiko Gemma, MD, PhD: Department of Pulmonary Medicine and Oncology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
Ichiro Yoshino, MD, PhD: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital, Narita, Japan
Toshihiro Misumi, PhD: Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan; Department of Data Science, National Cancer Center Hospital East, Chiba, Japan
Akito Hata, MD: Department of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Hyogo, Japan
Satoshi Hara, MD: Department of Respiratory Medicine, Itami City Hospital, Hyogo, Japan
Takashi Kijima, MD, PhD: Department of Respiratory Medicine and Hematology, Hyogo Medical University, Nishinomiya, Hyogo, Japan
Fujita Masaki, MD, PhD: Department of Respiratory Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
Shunichiro Iwasawa, MD, PhD: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Shintaro Nakagawa, MSc: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Masahiro Tatsuno, MSc: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Tetsuya Mitsudomi, MD, PhD: Kindai Hospital Global Research Alliance Center and Thoracic Surgery, Kindai University, Osaka, Japan; Corresponding author. Address for correspondence: Tetsuya Mitsudomi, MD, PhD, Kindai Hospital Global Research Alliance Center and Thoracic Surgery, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.

Journal volume & issue: Vol. 5, no. 7
p. 100683

Abstract

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Introduction: This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. Methods: A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). Results: Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. Conclusions: In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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