PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients

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 analysed 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. All cases with moderate or strong staining (2+/3+) in 45% of tumour cells were considered as positive. Results: PD-1 positive (+) was significantly associated with current smoking status (P = 0.02) and with the presence of KRAS mutations (P = 0.006), whereas 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+ vs PD-L1 negative in terms of the response rate (RR: P = 0.01) time to progression (TTP: P < 0.0001) and survival (OS: P = 0.09), with no difference in PD1+ vs 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). Conclusions: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.