Journal Article

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

Capodanno, A, Minuti, G, Crinò, L, Tibaldi, C, Landi, L, Tornillo, L, Salvini, J, Chella, A, Coppi, E, Cappuzzo, F, Terracciano, L, Rossi, E, Fontanini, G, Incensati, R M, D'Incecco, A, Filice, M E, Ludovini, V, Andreozzi, M, Sani, S

2015

Overview

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 >5% 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/699/67/1059/602 / 692/699/67/1612/1350 / Adult / Aged / Aged, 80 and over / B7-H1 Antigen - biosynthesis / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - pathology / Cohort Studies / Drug Resistance / Epidemiology / Female / Humans / Immunohistochemistry / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Male / Middle Aged / Molecular Medicine / Oncology / Programmed Cell Death 1 Receptor - biosynthesis / Retrospective Studies / Translational Therapeutics