High PD-L1 Expression and Clinical Outcomes of First-Line Osimertinib in

@article{yoshihikosakata2026high,
  title = {{High PD-L1 Expression and Clinical Outcomes of First-Line Osimertinib in}},
  author = {Yoshihiko Sakata, MD and Kenta Murotani, PhD and Daichi Fujimoto, MD, PhD and Yukihiro Toi, MD and Toshihide Yokoyama, MD and Seigo Katakura, MD, PhD and Teppei Yamaguchi, MD, PhD and Kaoru Tanaka, MD, PhD and Satoru Miura, MD, PhD and Motohiro Tamiya, MD and Motoko Tachihara, MD, PhD and Takehito Shukuya, MD, PhD and Yuko Tsuchiya, MD, PhD and Yuki Sato, MD, PhD and Satoshi Ikeda, MD, PhD and Shinya Sakata, MD, PhD and Takeshi Masuda, MD, PhD and Shinnosuke Takemoto, MD, PhD and Hirotsugu Kenmotsu, MD, PhD and Isamu Okamoto, MD, PhD and Nobuyuki Yamamoto, MD, PhD},
  journal = {JTO Clinical and Research Reports},
  year = {2026},
  month = jul,
  doi = {10.1016/j.jtocrr.2026.101054},
  url = {https://doi.org/10.1016/j.jtocrr.2026.101054},
  note = {CC BY-NC-ND 4.0},
}

TY  - JOUR
TI  - High PD-L1 Expression and Clinical Outcomes of First-Line Osimertinib in
AU  - Yoshihiko Sakata, MD
AU  - Kenta Murotani, PhD
AU  - Daichi Fujimoto, MD, PhD
AU  - Yukihiro Toi, MD
AU  - Toshihide Yokoyama, MD
AU  - Seigo Katakura, MD, PhD
AU  - Teppei Yamaguchi, MD, PhD
AU  - Kaoru Tanaka, MD, PhD
AU  - Satoru Miura, MD, PhD
AU  - Motohiro Tamiya, MD
AU  - Motoko Tachihara, MD, PhD
AU  - Takehito Shukuya, MD, PhD
AU  - Yuko Tsuchiya, MD, PhD
AU  - Yuki Sato, MD, PhD
AU  - Satoshi Ikeda, MD, PhD
AU  - Shinya Sakata, MD, PhD
AU  - Takeshi Masuda, MD, PhD
AU  - Shinnosuke Takemoto, MD, PhD
AU  - Hirotsugu Kenmotsu, MD, PhD
AU  - Isamu Okamoto, MD, PhD
AU  - Nobuyuki Yamamoto, MD, PhD
PY  - 2026
DA  - 2026/07/24
JO  - JTO Clinical and Research Reports
DO  - 10.1016/j.jtocrr.2026.101054
UR  - https://doi.org/10.1016/j.jtocrr.2026.101054
AB  - Introduction: Osimertinib is the standard first-line therapy for EGFR -mutated NSCLC. Nevertheless, the clinical significance of high programmed death-ligand 1 (PD-L1) expression in this setting remains unclear. This study aimed to evaluate the association between a high PD-L1 tumor proportion score (≥50%) and clinical outcomes in patients treated with first-line osimertinib. Methods: This multicenter retrospective study used the REAL-WIND database from 16 Japanese institutions. Among 486 patients with EGFR -mutated NSCLC treated with first-line osimertinib, 385 patients with known PD-L1 status formed the full cohort (cohort B). After excluding 185 patients who overlapped with the published OSI-FACT data set, 200 patients formed the non-overlapping validation cohort (cohort A). Patients were stratified by PD-L1 tumor proportion score (≥50% versus <50%). The primary end point was real-world progression-free survival (rwPFS), and secondary end points were overall survival (OS) and time to treatment failure. Outcomes were evaluated using unadjusted analyses and propensity score–based analyses to assess the robustness of the observed associations. Results: In cohort A, high PD-L1 expression was associated with shorter rwPFS (hazard ratio [HR] = 1.95, 95% confidence interval [CI]: 1.30–2.92, p = 0.001) and OS (HR = 1.72, 95% CI: 1.02–3.09, p = 0.044). Similar associations were observed in cohort B for rwPFS (HR = 1.76, 95% CI: 1.30–2.37, p < 0.001) and OS (HR = 1.92, 95% CI: 1.28–2.87, p = 0.002). These associations were consistent in unadjusted analyses and in propensity score–based analyses adjusting for baseline confounding, supporting the reproducibility of the findings in this real-world cohort. Conclusions: High PD-L1 expression was associated with reduced clinical benefit from first-line osimertinib in EGFR -mutated NSCLC. These findings should be interpreted as a consistent clinical association observed in real-world practice, rather than definitive evidence of a predictive biomarker.
SN  - 2666-3643
ER  -