• non-small-cell lung cancer
• PD-1
• PD-L1
• tyrosine kinase inhibitors

Background: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC.
Methods: We analyzed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild-type. PD-L1 and PD-1 expression were assessed by immunohistochemistry (IHC). All cases with moderate or strong staining (2+/3+) in >5% of cells were considered as positive.
Results: PD-1 positive (+) was significantly associated with current smoking status (p=0.02) and with presence of KRAS mutations (P=0.006), while PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ versus PD-L1 negative in terms of response rate (RR: P=0.01) time to progression (TTP: P<0.0001) and survival (OS: P=0.09), with no difference in PD1+ versus PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01).
Conclusion: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.