Targeting the PD-1/PD-L1 axis in the treatment of lung cancer

Abstract

In recent years major advances in the field of molecular profiling of non-small cell lung cancer led to the identification of targetable driver mutations and revolutionized the treatment of specific patient subsets. However, the majority of NSCLC tumors do not harbor these genomic events. On the other hand, current studies have confirmed an expanding role for immunotherapy in lung cancer and new agents, such as inhibitors of the programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis have been introduced in the treatment armamentarium. The monoclonal antibodies nivolumab and pembrolizumab targeting PD-1 resulted in superior survival when compared to standard second line chemotherapy within the context of randomized trials and received regulatory approval. Moreover, several other anti-PD-L1 antibodies have demonstrated encouraging preliminary efficacy and multiple clinical trials in various settings during the disease trajectory are currently underway. Early immunotherapy trials have also illustrated the potential of PD-1 blockade in small cell lung cancer treatment, a disease for which major advances in systemic therapy are lacking. The currently available clinical data on PD-1/PD-L1 inhibition in lung cancer are summarized in this review.