Shining light on advanced NSCLC in 2017: combining immune checkpoint inhibitors

The treatment landscape has changed since the immune checkpoint inhibitors were approved in the treatment of non-small cell lung cancer (NSCLC). Although the promising clinical benefit from programmed death-1/programmed death ligand-1 (PD-1/PD-L1) inhibitors was observed in the second or subsequent line treatment of patients who progressed on chemotherapy, it has a long way for single PD-1/PD-L1 inhibitor to move forward to the frontline without a predictive biomarker. Tumor response is far from satisfactory without selection and primary or acquired resistance to PD-1/PD-L1 inhibitors hampered their utility. Therefore, it is crucial to determine a strategy that can optimize the application of immune checkpoint inhibitors and increase the numbers of the responders. Multiple combination approaches based on PD-1/PD-L1 inhibitors are designed and aimed to boost anti-tumor response and benefit a broader population. In this review, we will integrate the updated clinical data to highlight the four most promising combination strategies in advance NSCLC: combination of checkpoint inhibition with chemotherapy, anti-angiogenesis, immunotherapy and radiotherapy. We further discuss the issues needed to be addressed and perspectives in the context of "combination era".