Immunotherapy targeting the PD-L1/PD-1 axis has recently shown spectacular efficacy and promise for the future of patients with metastatic
lung cancer. In the setting of second-line treatment of metastatic disease, this
therapy has increased overall survival of patients by several months when compared to
chemotherapy, both for
squamous cell carcinoma (SCC) and
adenocarcinoma (ADC) of the lung. Clinical trials targeting the PD-1/PD-L1 axis have shown a tendency towards higher efficacy if expression of PD-L1 is relatively high, as evaluated by immunohistochemistry (IHC) of tumour samples. Targeting the PD-1/PD-L1 axis is of crucial importance not only for metastatic
non-small cell lung cancer (NSCLC) but probably also for patients with
small cell lung cancer.
Nivolumab, an antibody targeting PD-1, has recently received FDA and EMA approval for NSCLC, regardless of the PDL1 expression status (for both tumour types in the USA and for only SCC in EU). However, the need for a
biomarker that allows better selection of patients is essential, to improve treatment efficacy and to manage cost of these
therapies. Assessment of PD-L1 expression through immunohistochemical staining is advocated by many as one such potential
biomarker. This prospect raises several questions, in particular how to define a threshold for positive PD-L1 labelling on biopsy tissue samples, taking into account that certain patients respond to treatment targeting PD-L1/PD-1, despite low or absent immunoreactivity of this
biomarker. This review discusses major challenges related to detection of PD-L1 by immunohistochemistry as a companion diagnostic test, along with
immune checkpoint blockade treatment of
lung cancer.