B7-H1/PD-1 Blockade Therapy in Non-Small Cell Lung Cancer Current Status and Future Direction

Over the past few years, there has been a mounting enthusiasm around the potential of immunotherapy in the treatment of non-small cell lung cancer (NSCLC). This interest was catalyzed in 2012 by initial reports of responses to programmed death 1 (PD-1) pathway inhibition in patients with heavily pretreated advanced NSCLC. Since then, a number of antibodies targeting either PD-1 or the primary ligand of PD-1, programmed death ligand 1 (PD-L1), have shown durable responses in phase I studies with large NSCLC expansion cohorts. Therapies have been well tolerated, with rare severe autoimmune toxicity. Two phase III trials have completed accrual in pretreated NSCLC patients, with a phase III trial underway in chemotherapy-naive patients with advanced NSCLC. Efforts are now focusing on identifying predictive biomarkers such as tumor PD-L1 expression and combinations of PD-1/PD-L1 inhibitors with either standard therapies for advanced NSCLC or other immunotherapies. This review summarizes clinical trial results to date and discusses challenges with ongoing and future clinical trials evaluating this new class of drugs.