PD-1/PD-L1 checkpoint blockades in non-small cell lung cancer: New development and challenges

Abstract

PD-1/PD-L1 checkpoint blockades have dramatically changed the landscape for second-line treatment of non-small cell lung cancer (NSCLC). Based on the promising results of Keynote-024 presented so far, pembrolizumab has been approved as first-line treatment for advanced PD-L1 positive NSCLC patients. However, overall response rate (ORR) is limited to PD-1/PD-L1 checkpoint blockades when used as single agent. Combining with chemotherapy, anti-CTLA-4 antibodies, targeted therapy, radiotherapy or other treatment options is perceived as an appealing method aimed at achieving higher efficacy. There are many clinical trials on going or finished assessing the efficacy and safety of the PD-1/PD-L1 blockades alone or combining with other approaches in first-line or second-line treatments. A lot of challenges need to be overcome before PD-1/PD-L1 checkpoint blockades are widely used in the patients with NSCLC including the identification of optimal combination, treatment-related adverse effects, the high cost and lack of effective predictive markers. In this review, we focus on outlining current clinical trials and challenges for future research of PD-1/PD-L1 pathway checkpoint blockades in NSCLC.