Clinical Efficacy and Safety of First- or Second-Generation EGFR-TKIs after Osimertinib Resistance for EGFR Mutated Lung Cancer: A Prospective Exploratory Study

Kenji Morimoto, Tadaaki Yamada, Takayuki Takeda, Shinsuke Shiotsu, Koji Date, Nobuyo Tamiya, Yasuhiro Goto, Hibiki Kanda, Yusuke Chihara, Yusuke Kunimatsu, Yuki Katayama, Masahiro Iwasaku, Shinsaku Tokuda, Koichi Takayama

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Osimertinib monotherapy is a common treatment for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC); however, standard treatment strategies for acquired resistance to this drug have not been established. In addition, the clinical significance of first-generation (1G) or second-generation (2G) EGFR-tyrosine kinase inhibitors (TKI) in patients with EGFR-mutant NSCLC and osimertinib resistance has not yet been fully evaluated. Objective: We aimed to conduct a prospective multicenter observational study to evaluate the efficacy and safety of 1G and 2G EGFR-TKIs after the development of osimertinib resistance. Methods: Patients with EGFR-mutant NSCLC who received 1G or 2G EGFR-TKIs after developing resistance to osimertinib monotherapy were prospectively assessed at eight institutions in Japan. The primary endpoint was progression-free survival (PFS). Results: A total of 29 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. The objective response and disease control rates were 6.9% (2/29) and 58.6% (17/29), respectively. The median PFS was 1.9 months [95% confidence interval (CI): 1.3–5.3]. There was no significant difference in PFS between the 1G and 2G EGFR-TKI groups (3.7 versus 1.5 months, log-rank test p = 0.20). However, patients with normal cytokeratin 19 fragment (CYFRA 21-1) and pro-gastrin-releasing peptide (ProGRP) levels experienced longer PFS than those with elevated CYFRA 21-1 and/or ProGRP (5.5 versus 1.3 months, log-rank test p < 0.001). Conclusion: Administration of 1G or 2G EGFR-TKIs after the development of osimertinib resistance has limited efficacy in patients with EGFR-mutant NSCLC. Moreover, normal CYFRA 21-1 and ProGRP levels could be promising indicators for 1G and 2G EGFR-TKI administration after osimertinib resistance development. Trial Registration Number: UMIN000044049.

Original languageEnglish
Pages (from-to)657-665
Number of pages9
JournalTargeted Oncology
Volume18
Issue number5
DOIs
Publication statusPublished - 09-2023

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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