Real-world efficacy of osimertinib in previously EGFR-TKI treated NSCLC patients without identification of T790M mutation

Yung Hung Luo, Han Liu, Jason A. Wampfler, Henry D. Tazelaar, Yalun Li, Tobias Peikert, Dan Liu, Konstantinos Leventakos, Yuh Min Chen, Yanan Yang, Shih Hwa Chiou, Ping Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice. Patients and methods: 417 patients had stage III–IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed. Results: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2–4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236). Conclusions: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.

Original languageEnglish (US)
Pages (from-to)2099-2114
Number of pages16
JournalJournal of Cancer Research and Clinical Oncology
Volume148
Issue number8
DOIs
StatePublished - Aug 2022

Keywords

  • EGFR mutation
  • Lung cancer
  • Osimertinib
  • PD-L1
  • T790M

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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