Strong PD-L1 Expression Predicts Poor Response and de Novo Resistance to EGFR TKIs Among NSCLC Patients With EGFR Mutation.

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This study retrospectively evaluated whether tumor expression of PD-L1 could predict the response of EGFR-mutated NSCLC to EGFR TKI therapy in 101 patients. Strong PD-L1 expression significantly decreased the objective response rate compared with weak or negative PD-L1 expression (35.7% vs 63.2% vs 67.3%; P = .002) and shortened progression-free survival (3.8 vs 6.0 vs 9.5 months; P < .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% vs 30.2%; P = .009). A high proportion of PD-L1 and CD8 dual–positive cases was found among patients with de novo resistance (46.7%; 7/15).

This study demonstrates 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 PD-L1 blockade.

https://www.jto.org/article/S1556-0864(18)30811-6/pdf