Abstract
BackgroundsEGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor.ResultsTPS≥1% for PD-L1 and low CD8+ TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40.5%), with 10 (21.2%) showing higher levels in the resistant biopsy (cohort B). Among the post-TKI high TPS groups, median PFS with low post- TKI CD8+ TIL scores treated with EGFR-TKIs (6.6 months) was significantly lower than that for the other patients (14.2 months; P = 0.015).ConclusionsThe change of PD-L1 expression was accompanied by dynamic change in CD8+ TILs and might reflect diverse mechanism of resistance to EGFR-TKI therapy.Material and MethodsWe identified 69 patients (cohort A) with sufficient post-TKI tumor tissues and 47 patients (cohort B) with paired tumor tissues available. TPS for PD-L1 expression of tumor cells and CD8+ TILs score in tumor specimens were determined by immunohistochemistry.
Highlights
Activating mutants of epidermal growth factor receptor (EGFR) are found in 40% of non-small cell lung cancer (NSCLC) patients in Asia and 10% of patients in Western countries [1]
The change of PD-L1 expression was accompanied by dynamic change in CD8+ tumor-infiltrating lymphocytes (TILs) and might reflect diverse mechanism of resistance to EGFR-tyrosine kinase (TKI) therapy
Treatment outcome in EGFRmutant NSCLC has been shown to outperform that in other lung cancers owing to the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) [2, 3]
Summary
Activating mutants of epidermal growth factor receptor (EGFR) are found in 40% of non-small cell lung cancer (NSCLC) patients in Asia and 10% of patients in Western countries [1]. Treatment outcome in EGFRmutant NSCLC has been shown to outperform that in other lung cancers owing to the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) [2, 3]. Resistance to third-generation TKIs, which target the resistance mutation T790M in exon 20 acquired in response to first-generation EGFR-TKIs, inevitably develops within 8–10 months [5, 6]. These observations www.impactjournals.com/oncotarget highlight the need to develop new treatment strategies, including immunotherapeutics. Patients with EGFR-TKI resistant EGFRmutant NSCLC with high tumor PD-L1 expression, but without the EGFR exon 20 T790M mutation, have shown favorable efficacy in nivolumab therapy [15]
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