PDL1-status predicts primary resistance of metastatic, EGFR-mutated non small cell lung cancers to EGFR tyrosine-kinase inhibitors

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BackgroundEGFR tyrosine-kinase inhibitors (TKIs) are the reference treatment for metastatic, EGFR-mutated, non-small-cell lung cancers (EGFRm NSCLCs). However, 16–20% of those tumors progress early (3–6 months) and factors predicting that resistance are unknown. This study was undertaken to examine PDL1 status as such a factor. MethodsThis retrospective analysis included metastatic, EGFRm-NSCLC patients who received first-line 1st-, 2nd- or 3rd-generation EGFR TKIs with PDL1 expression determined in pretreatment biopsies. Kaplan–Meier estimations of probabilities of progression-free survival (PFS) and overall survival (OS) were compared with log-rank test, and logistic-regression analyses. ResultsPDL1 status of the 145 included patients was ≥1% (47%), 1–49% (33%) or ≥50% (14%). For PDL1-positive vs PDL1-negative patients, respectively, median PFS lasted 8 (95% CI: 6–12) vs 12 (95% CI: 11–17) months (p = 0.008), with 18% vs. 8% (NS) of NSCLCs progressing at 3 months, and 47% vs. 18% (HR 0.25 [95% CI 0.10–0.566], p<0.001) at 6 months. Multivariate analysis retained 1st- or 2nd-generation EGFR TKI, brain metastases and albuminemia <35 g/L at diagnosis as significantly associated with shorter PFS, but not PDL1 status, which was independently associated with progression at 6 months (HR 3.76 [1.23–12.63], p = 0.02). PDL1-negative and PDL1-positive patients’ OS lasted 27 (95% CI 24–39) and 22 (95% CI 19–41) months, respectively (NS). Multivariate analysis retained only brain metastases or albuminemia <35 g/L at diagnosis as being independently associated with OS. ConclusionPDL1 expression ≥1% seems to be associated with early progression during the first 6 months of first-line EGFR-TKI treatment of metastatic EGFRm NSCLCs, without impacting OS.