PD-1, PD-L1 differentially expressed in NSCLC

Dec 9 2014

By Shreeya Nanda, Senior medwireNews Reporter

The expression of the immune checkpoint protein programmed death-1 receptor (PD-1) and its ligand (PD-L1) varies according to tumour and patient characteristics in oncogene-addicted non-small-cell lung cancer (NSCLC), research indicates.

Additionally, PD-L1 expression correlated with clinical outcomes in response to treatment with epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs), leading the researchers to comment that the differential expression could modulate sensitivity to targeted agents.

Federico Cappuzzo (Istituto Toscano Tumori, Livorno, Italy) and co-workers investigated whether PD-1 and PD-L1 were differentially expressed in patients with NSCLC according to the presence or absence of mutations in the EGFR and Kirsten rat sarcoma viral oncogene homologue (KRAS) genes and anaplastic lymphoma kinase (ALK) rearrangements.

PD-1 and PD-L1 expression was assessed by immunohistochemistry in tumour samples from 125 patients with metastatic NSCLC, of whom 56 had EGFR mutations, 29 harboured KRAS mutations, 10 had ALK translocations and 30 were wild-type for all three genes. Cases were considered positive for PD-1 or PD-L1 if more than 5% of tumour cells had moderate or strong staining.

A total of 43 and 68 samples were positive for PD-1 and PD-L1 expression, respectively. PD-1 positive status correlated significantly with presence of KRAS mutations and current smoking status, whereas PD-L1 positivity was significantly associated with the presence of EGFR mutations and adenocarcinoma histology.

In the 99 patients who had been treated with the EGFR–TKIs gefitinib or erlotinib, PD-L1, but not PD-1, positivity was associated with improved outcomes. Patients positive for PD-L1 expression had a significantly higher response rate (61.2 vs 34.8%) and a significantly prolonged time to progression (11.7 vs 5.7 months) compared with PD-L1 negative individuals. Overall survival was also extended in PD-L1–positive patients, at 21.9 months compared with 12.5 months in PD-L1–negative patients, but this difference was not significant.

When just the patients with EGFR mutations were considered, only time to progression was significantly improved in PD-L1–positive versus PD-L1–negative patients, at 13.1 versus 8.5 months, in response to EGFR–TKI treatment.

“Our findings represent the rationale to choose a different checkpoint inhibitor according to the tumour driver and to combine targeted therapies with anti-PD-L1 or anti-PD-1 agents”, the researchers conclude in the British Journal of Cancer.

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