PMID- 34589912
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 2666-3643 (Electronic)
IS  - 2666-3643 (Linking)
VI  - 1
IP  - 1
DP  - 2020 Mar
TI  - The Long Half-Life of Programmed Cell Death Protein 1 Inhibitors May Increase the 
      Frequency of Immune-Related Adverse Events After Subsequent EGFR Tyrosine Kinase 
      Inhibitor Therapy.
PG  - 100008
LID - 10.1016/j.jtocrr.2020.100008 [doi]
LID - 100008
AB  - INTRODUCTION: EGFR tyrosine kinase inhibitors are one of the key drugs for 
      treatment of NSCLC with EGFR mutations. In recent times, immune check-point 
      inhibitors (ICIs) have also been widely used for patients with NSCLC. Although a 
      subset of patients obtain benefit from ICIs, adverse events (AEs) that are 
      different from those of cytotoxic chemotherapies may occur. Moreover, some 
      patients develop AEs, which seem to be caused by the previously discontinued 
      nivolumab. METHODS: We identified patients with NSCLC who developed AEs, which 
      started shortly after discontinuation of nivolumab and during treatment with 
      osimertinib. We conducted liquid chromatography-mass spectrometry analyses to 
      estimate the concentration of serum nivolumab. RESULTS: Three patients with AEs 
      were identified. Two patients developed interstitial lung disease (cases 1 and 2) 
      and one developed hepatotoxicity (case 3) during osimertinib therapy initiated 
      after nivolumab administration. They received several treatments, including 
      cytotoxic chemotherapies or EGFR tyrosine kinase inhibitors other than 
      osimertinib, followed by nivolumab for three to five cycles; nevertheless, the 
      disease progressed. After discontinuation of nivolumab, osimertinib was 
      administered from day 22 to 46; but treatment-related toxicities developed 56 to 
      96 days later. Liquid chromatography-mass spectrometry analyses revealed that the 
      remaining levels of nivolumab in the blood (2.1 mug/mL, 12.8 mug/mL, and 31.1 
      mug/mL, respectively, for cases 1, 2, and 3) were enough to induce an immune 
      response. CONCLUSION: The presence of the ICI antibody that persists even after 
      drug discontinuation may account not only for the prolonged efficacy of these 
      agents but also for the late onset of AEs, especially when the antibodies may 
      have interacted during subsequent treatments.
CI  - (c) 2020 The Authors.
FAU - Shinno, Yuki
AU  - Shinno Y
AD  - Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, 
      Chuo-ku, Tokyo, Japan.
FAU - Goto, Yasushi
AU  - Goto Y
AD  - Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, 
      Chuo-ku, Tokyo, Japan.
FAU - Ohuchi, Mayu
AU  - Ohuchi M
AD  - Division of Molecular Pharmacology, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan.
FAU - Hamada, Akinobu
AU  - Hamada A
AD  - Division of Clinical Pharmacology and Translational Research, Exploratory 
      Oncology Research and Clinical Trial Center, National Cancer Center, Tsukiji, 
      Chuo-ku, Tokyo, Japan.
FAU - Nokihara, Hiroshi
AU  - Nokihara H
AD  - Department of Respiratory Medicine and Rheumatology, Graduate School of 
      Biomedical Sciences, Tokushima University, Kuramoto-cho, Tokushima, Tokushima, 
      Japan.
FAU - Fujiwara, Yasuhiro
AU  - Fujiwara Y
AD  - Department of Breast and Medical Oncology, National Cancer Center Hospital, 
      Tsukiji, Chuo-ku, Tokyo, Japan.
FAU - Ohe, Yuichiro
AU  - Ohe Y
AD  - Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, 
      Chuo-ku, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200211
PL  - United States
TA  - JTO Clin Res Rep
JT  - JTO clinical and research reports
JID - 101769967
PMC - PMC8474461
OTO - NOTNLM
OT  - EGFR
OT  - Immune-related adverse events
OT  - Non-small cell lung cancer
OT  - Osimertinib
OT  - programmed cell death protein 1
EDAT- 2020/02/11 00:00
MHDA- 2020/02/11 00:01
PMCR- 2020/02/11
CRDT- 2021/09/30 07:21
PHST- 2020/01/14 00:00 [received]
PHST- 2020/01/15 00:00 [accepted]
PHST- 2021/09/30 07:21 [entrez]
PHST- 2020/02/11 00:00 [pubmed]
PHST- 2020/02/11 00:01 [medline]
PHST- 2020/02/11 00:00 [pmc-release]
AID - S2666-3643(20)30008-4 [pii]
AID - 100008 [pii]
AID - 10.1016/j.jtocrr.2020.100008 [doi]
PST - epublish
SO  - JTO Clin Res Rep. 2020 Feb 11;1(1):100008. doi: 10.1016/j.jtocrr.2020.100008. 
      eCollection 2020 Mar.