Combinational immunotherapy based on immune checkpoints inhibitors in small cell lung cancer: is this the beginning to reverse the refractory situation?

Small cell lung cancer (SCLC), a particular neuroendocrine tumor, occupies 13% of lung cancers, with the highest mortality among cancers. Immune checkpoints inhibitors (ICIs) based on programmed cell death protein-1 (PD-1)/programmed cell death one ligand (PD-L1) inhibitors and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors have been one of the most favorable therapies in SCLC. Simultaneously, not all the patients respond to ICIs due to the lack of biomarkers to predict the immunotherapeutic effect. Multiple combinational approaches are under exploration, including the integrated or successive assessment of additional immunotherapeutic agents, chemotherapy, radiotherapy, and targeted therapy with ICIs. The current review offers a general view of the rationale for clinical studies exploring the experimental result of combinational immunotherapy based on ICIs, with both available results and ongoing trials. Moreover, the development of more predictive biomarkers, specific clinical trial designs, enhancement of the efficacy, and decreasing the financial toxicity will become the trend of future research and clinical applications of ICIs. Understanding the evolving immuno-oncology is increasingly relevant and crucial to solve those problems and define therapeutic strategies and potential target populations of combinational immunotherapy. Ultimately, emerging combinational immunotherapy will transform SCLC into a chronic disease to help patients survive from tumors.