High PD-L1 expression linked to reduced survival in NSCLC

Aug 28 2014

By Laura Cowen, medwireNews Reporter

Overexpression of programmed death-ligand 1 (PD-L1) is independently associated with the presence of epidermal growth factor receptor (EGFR) gene mutations and poor prognosis in patients with non-small-cell lung cancer (NSCLC), Japanese researchers report.

Isamu Okamoto (Kyushu University Hospital, Fukuoka) and colleagues explain that the binding of PD-L1 to its corresponding protein PD1 induces apoptosis in activated T-cells, but blocking this interaction can enhance T-cell antitumour activity.

Indeed, recent clinical trials have shown that blockade of the PD1–PD-L1 interaction with specific antibodies yields a clinical response in a subset of individuals with advanced NSCLC.

To investigate the clinical relevance of PD-L1 expression, Okamoto and team analysed completely resected tumour specimens from 164 patients with NSCLC by immunohistochemistry.

They report in the Annals of Oncology that expression of PD-L1 was significantly higher in tumour specimens from women than men, from never smokers than smokers, in patients with adenocarcinoma rather than squamous cell carcinoma and in those positive for EGFR mutations versus those with wild-type EGFR.

In multivariate analyses, the presence of EGFR mutations and adenocarcinoma histology were significantly and independently associated with increased PD-L1 expression.

Consistent with these findings, Okamoto and team also showed that PD-L1 expression, detected by flow cytometry, was significantly higher in NSCLC cell lines positive for EGFR mutations than in those with wild-type EGFR.

Furthermore, inhibition of EGFR signalling with erlotinib resulted in downregulation of PD-L1 expression in EGFR mutation-positive NSCLC cells but not in those with wild-type EGFR, “indicating that the expression of PD-L1 is likely dependent on EGFR signaling conferred by activating EGFR mutations”, the researchers remark.

In terms of prognosis, the investigators found that patients with high (above median) tumour PD-L1 expression had a significantly shorter overall survival than those with low expression, at a median of 55.9 versus 72.6 months.

And Cox regression analysis confirmed that high PD-L1 expression, as well as advanced stage (II or III), was significantly and independently associated with a shorter overall survival.

Taken together, “[t]hese data suggest that therapeutic blockade of the PD1–PD-L1 pathway may enhance the efficacy of treatment of EGFR mutation-positive NSCLC”, say Okamoto et al.

They conclude that, despite the relatively small sample and retrospective nature of the study, their results “provide a rationale for future clinical investigations of the PD1–PD-L1 axis as a target for adjuvant chemotherapy in individuals with NSCLC whose resected tumors are found to have a high expression score for PD-L1.”

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