PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction?

Abstract

Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing. Despite impressive treatment outcomes in a subset of patients who receive these immune therapies, many patients with NSCLC fail to respond to anti-PD-1/PD-L1 and the identification of a biomarker to select these patients remains highly sought after. In this review, we discuss the recent clinical trial results of pembrolizumab, nivolumab, and atezolizumab for NSCLC, and the significance of companion diagnostic testing for tumor PD-L1 expression.

Keywords: Biomarker; Immune checkpoint inhibitor; Immunotherapy; Lung cancer; NSCLC; Nivolumab; PD-1; PD-L1; Pembrolizumab.

Fig. 1

PD-L1 proportion scores and their relationship to objective response rates to pembrolizumab in KEYNOTE 001 and KEYNOTE 010