Related Experiment Video
Updated: Jun 4, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
PD-L1 expression and immune profiling cannot predict osimertinib efficacy in lung cancer with EGFR T790 M mutation: A
Ching-Yao Yang1, Wei-Yu Liao1, Chao-Chi Ho1
1Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Background:
PD-L1 is associated with poor efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in untreated EGFR-mutant non-small-cell lung cancer (NSCLC). Whether PD-L1 is also predictive of osimertinib efficacy in pre-treated patients with an acquired EGFR T790 M mutation is unclear.
Patients And Methods:
PD-L1 expression and tumor microenvironments were evaluated in tumors from EGFR-mutant T790 M + NSCLC patients treated with osimertinib. In vitro and in vivo experiments were also performed to examine the effect of PD-L1 overexpression on osimertinib susceptibility in EGFR T790 M + cells.
Results:
A total of 134 pre-treated EGFR T790 M + patients were enrolled, of whom 72 had del19, 58 had L858R, and 4 had G719X as initial EGFR mutation subtype. Positive PD-L1 expression (TC ≥ 1%) was found in 21 of 134 (15.7%) patients. PD-L1 expression did not differ across different biopsied sites and among different EGFR mutation subgroups. Kaplan-Meier estimate revealed no significant difference in progression-free survival (PFS) in PD-L1-positive versus PD-L1-negative patients. Multivariate analysis using the Cox proportional hazard model found that older age and L858R mutation were independent predictive factors. Multiplex IHC showed that immune cell infiltration was not associated with PD-L1 expression or osimertinib treatment response. By overexpressing PD-L1 in EGFR T790 M + cells, we found that PD-L1 did not result in osimertinib resistance in in vitro and xenograft models.
Conclusion:
PD-L1 expression in pre-treated EGFR T790 M + lung adenocarcinoma is not predictive of osimertinib efficacy, as demonstrated by in vitro, xenograft, and clinical case studies.
Insights
Programmed death-ligand 1 (PD-L1) expression does not predict osimertinib efficacy in pre-treated non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutations. This finding was consistent across clinical, in vitro, and xenograft studies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Programmed death-ligand 1 (PD-L1) is linked to poor outcomes with first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in untreated EGFR-mutant NSCLC.
- The predictive value of PD-L1 for osimertinib efficacy in pre-treated patients with acquired EGFR T790M mutations remains undetermined.
Purpose of the Study:
- To investigate the association between PD-L1 expression and osimertinib efficacy in pre-treated EGFR T790M-mutant NSCLC patients.
- To explore the role of PD-L1 in osimertinib resistance using in vitro and in vivo models.
Main Methods:
- PD-L1 expression and tumor microenvironments were analyzed in 134 pre-treated EGFR T790M-mutant NSCLC patients receiving osimertinib.
- In vitro and xenograft models were used to assess the impact of PD-L1 overexpression on osimertinib susceptibility.
Main Results:
- PD-L1 expression (TC ≥ 1%) was observed in 15.7% of patients and did not correlate with biopsy site or EGFR mutation subtype.
- No significant difference in progression-free survival (PFS) was found between PD-L1-positive and PD-L1-negative patients.
- In vitro and xenograft studies indicated that PD-L1 overexpression did not confer osimertinib resistance.
Conclusions:
- PD-L1 expression is not a predictive biomarker for osimertinib efficacy in pre-treated EGFR T790M-mutant lung adenocarcinoma.
- Findings were supported by clinical data, in vitro experiments, and xenograft models.
