Abstract
Introduction: One mechanism by which tumor cells are thought to evade the host’s immune system is by inducing negative signals that cause T-cell suppression. An important interaction that results in this phenomenon is the one between programmed death-1 (PD-1) on the T cell and its ligand PD ligand-1 (PD-L1) on the tumor cell. PD-1 pathway blocking agents, such as nivolumab, are therefore capable of reversing T-cell suppression and ultimately induce antitumor responses.
Areas covered: In this review, the authors summarize investigations related to the safety and efficacy of nivolumab in a variety of malignancies thus far, including advanced melanoma, renal cell carcinoma (RCC) and NSCLC.
Expert opinion: The results have been promising with a large number of objective responses and favorable safety profiles inspiring several Phase III trials in these settings. More recent studies are exploring the role of this drug in the treatment of various other cancers. Combination therapies involving nivolumab are also being studied and are yielding interesting results. Finally, the role of tumor PD-L1 expression as a predictive biomarker remains to be ascertained. Thus, with rational refinement through biomarker and combination clinical trials, nivolumab and other PD-1 blocking agents will likely lead to significant improvements in cancer therapeutics.
Declaration of interest
DF McDermott has acted as a consultant for Bristol-Myers Squibb, Roche, Merck & Co. and Pfizer, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.