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Br J Cancer. 2015 Jan 6;112(1):95-102. doi: 10.1038/bjc.2014.555. Epub 2014 Oct 28.

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

Author information

1
Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
2
Department of Pathology, Basel Hospital University, Schönbeinstrasse 40, 4003 Basel, Switzerland.
3
Division of Medical Oncology, Santa Maria della Misericordia Hospital, Località S. Andrea delle Fratte 1, 06134 Perugia, Italy.
4
Azienda Ospedaliero-Universitaria Pisana, University Hospital, via Roma 57, 56126 Pisa, Italy.
5
Department of Surgical, Medical, Molecular Pathology and Critical Area, Pisa University, via Roma 57, 56126 Pisa, Italy.

Abstract

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.

PMID:
25349974
PMCID:
PMC4453606
DOI:
10.1038/bjc.2014.555
[Indexed for MEDLINE]
Free PMC Article

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