A phase I/II study of osimertinib in EGFR exon 20 insertion mutation-positive non-small cell lung cancer

Hiroyuki Yasuda, Eiki Ichihara, Jun Sakakibara-Konishi, Yoshitaka Zenke, Shinji Takeuchi, Masahiro Morise, Katsuyuki Hotta, Mineyoshi Sato, Shingo Matsumoto, Azusa Tanimoto, Reiko Matsuzawa, Katuyuki Kiura, Yuta Takashima, Seiji Yano, Junji Koyama, Takahiro Fukushima, Junko Hamamoto, Hideki Terai, Shinnosuke Ikemura, Ryo TakemuraKoichi Goto, Kenzo Soejima

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Objectives: Several preclinical data proposed a potential efficacy of osimertinib, a third-generation EGFR tyrosine kinase inhibitor, for EGFR exon 20 insertion (EGFR ex20ins)-positive non-small cell lung cancer (NSCLC). However, reported case series and a retrospective study proposed controversial efficacy. The efficacy of osimertinib in EGFR ex20ins-positive NSCLC have not been well evaluated in prospective clinical trials. In this study, we performed a prospective, single-arm, multi-center, open-label, non-randomized phase I/II study to evaluate efficacy of osimertinib for EGFR ex20ins-positive NSCLC. Materials and methods: From August 2018 to January 2020, 14 NSCLC patients with EGFR ex20ins were enrolled, of whom 2 were excluded because they did not meet the inclusion criteria. Efficacy and safety of 80 mg osimertinib were evaluated. In addition, we performed a translational exploratory study to clarify the association of mutation type-specific drug sensitivity, osimertinib pharmacokinetic data, and clinical efficacy. Results: Of the evaluated patients, none experienced objective response, 7 experienced stable disease (58.3%), and 5 experienced disease progression (41.7%). The median progression free survival (PFS) was 3.8 months, and the median overall survival was 15.8 months. Interestingly, the exploratory study demonstrated statistically significant positive correlation between plasma osimertinib concentration/in vitro IC50 ratio and PFS (R = 0.9912, P = 0.0001), highlighting the mutation type-specific concentration-dependent efficacy of osimertinib for EGFR ex20ins-positive NSCLC. Conclusions: Regular dose, 80 mg/day, of osimertinib has limited clinical activity in NSCLC patients with EGFR ex20ins. The translational study proposed the potential efficacy of higher dose osimertinib in a subgroup of EGFR ex20ins-positive NSCLC.

Original languageEnglish
Pages (from-to)140-146
Number of pages7
JournalLung Cancer
Publication statusPublished - Dec 2021


  • EGFR exon 20 insertion
  • IC
  • Non-small cell lung cancer
  • Osimertinib
  • Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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