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Programmed death-ligand 1 expression according to epidermal growth factor receptor mutation status in pretreated non-small cell lung cancer.


ABSTRACT: Current clinical trials have suggested poorer efficacies of anti-programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, implying lower PD-L1 expression in EGFR-mutant NSCLC than in EGFR-wild type.We retrospectively analyzed correlation between PD-L1 expression and EGFR status in clinical samples of pretreated NSCLC. PD-L1 immunohistochemistry was performed using the 28-8 anti-PD-L1 antibody for tumor cell membrane staining. H-score was adopted to evaluate both percentage and intensity. We investigated H-scores ?1, ?5, and ?10 as PD-L1+ cut-offs. H-score ?10 was defined as strong PD-L1+.We investigated 96 available histologic samples in 77 pretreated patients with NSCLC. Median H-score in EGFR-mutant samples (n=65) was 3 (range, 0-150), whereas EGFR-wild-type (n=31) was 8 (range, 0-134) (p=0.0075). Using H-scores ?1, ?5, and ?10 cut-offs, incidence of PD-L1+ in EGFR-mutant vs. EGFR-wild-type samples were: 85% (55/65) vs. 94% (29/31) (p=0.2159); 42% (27/65) vs. 74% (23/31) (p=0.0027); and 22% (14/65) vs. 48% (15/31) (p=0.0074), respectively. Patient-oriented (n=77) univariate analysis for strong PD-L1+ found age of sample (p=0.0226) and EGFR mutation status (p=0.0490) as significant factors. Multivariate analysis identified EGFR mutation status as the only significant factor (p=0.0121, odds ratio 2.99) for strong PD-L1+. H-scores of PD-L1 expression varied in all 11 cases receiving multiple rebiopsies, and categories of positivity migrated in 10 (91%) of 11 patients.PD-L1 expression was significantly lower in EGFR-mutant NSCLC samples than in EGFR wild-type samples. Its expression could be dynamic and affected by age of sample.

SUBMITTER: Hata A 

PROVIDER: S-EPMC5768364 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Programmed death-ligand 1 expression according to epidermal growth factor receptor mutation status in pretreated non-small cell lung cancer.

Hata Akito A   Katakami Nobuyuki N   Nanjo Shigeki S   Okuda Chiyuki C   Kaji Reiko R   Masago Katsuhiro K   Fujita Shiro S   Yoshida Hiroshi H   Zama Kota K   Imai Yukihiro Y   Hirata Yukio Y  

Oncotarget 20171201 69


<h4>Background</h4>Current clinical trials have suggested poorer efficacies of anti-programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (<i>EGFR</i>) mutations, implying lower PD-L1 expression in <i>EGFR</i>-mutant NSCLC than in <i>EGFR</i>-wild type.<h4>Methods</h4>We retrospectively analyzed correlation between PD-L1 expression and <i>EGFR</i> status in clinical samples of pretreated NSCLC. PD-L1 immuno  ...[more]

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