Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1 or CD279) have noticeably improved the treatment landscape of advanced cancer patients. Nivolumab, the most well-known genetically engineered anti-PD-1 monoclonal antibody (mAb), promotes anti-tumor immunity and shows excellent capability for treating various cancers, particularly lung cancer, renal cancer, and melanoma. Systemic administration of nivolumab could inspire durable therapeutic responses not typically seen with traditional cytotoxic anti-cancer agents. However, nivolumab monotherapy is ineffective in 60-70 percent of patients. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and multifactorial. Recently, the rationality of adding other conventional therapies such as chemo-radiotherapy and targeted therapies such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and VEGF/VEGFR inhibitors to nivolumab has strongly been verified. These regimens overcome cancer resistance and thus boost nivolumab efficacy in cancer patients. Herein, we discuss the current status of the combination therapy with nivolumab in cancer patients, with a particular focus on the recent clinical reports.