LAUSR

Introduction: This study evaluated whether tumor expression of programmed death ligand 1 (PD‐L1) could predict the response of EGFR‐mutated NSCLC to EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: We retrospectively evaluated patients who received EGFR‐TKIs for advanced NSCLC at the Guangdong Lung Cancer Institute between April 2016 and September 2017 and were not enrolled in clinical studies. The patients' EGFR and PD‐L1 statuses were simultaneously evaluated. Results: Among the 101 eligible patients, strong PD‐L1 expression significantly decreased objective response rate, compared with weak or negative PD‐L1 expression (35.7% versus 63.2% versus 67.3%, p = 0.002), and shortened progression‐free survival (3.8 versus 6.0 versus 9.5 months, p < 0.001), regardless of EGFR mutation type (19del or L858R). Furthermore, positive PD‐L1 expression was predominantly observed among patients with de novo resistance rather than acquired resistance to EGFR‐TKIs (66.7% versus 30.2%, p = 0.009). Notably, we found a high proportion of PD‐L1 and cluster of differentiation 8 (CD8) dual‐positive cases among patients with de novo resistance (46.7%, 7 of 15). Finally, one patient with de novo resistance to EGFR‐TKIs and PD‐L1 and CD8 dual positivity experienced a favorable response to anti–programmed death 1 therapy. Conclusions: This study revealed the adverse effects of PD‐L1 expression on EGFR‐TKI efficacy, especially in NSCLC patients with de novo resistance. The findings indicate the reshaping of an inflamed immune phenotype characterized by PD‐L1 and CD8 dual positivity and suggest potential therapeutic sensitivity to programmed death 1 blockade.