Molecular targeted therapy for the treatment of renal cancer: Current state and issues

In this article, we review the issues related to molecular targeted therapy for the treatment of renal cancer. In Japan, molecular targeted-based agents have been approved for use since 2008. There are two types of molecular targeted-based agents, and there are 5 targeted-based agents currently available, these being 3 vascular endothelial growth factor receptor tyrosine kinase inhibitors and 2 mammalian target of rapamycin inhibitors. Regarding the clinical use of molecular targeted agents, their positioning in metastatic renal cancer treatment is listed in Table 1. For the most part, the positioning of the agents has been determined by the results of a Phase III randomized control study (RCT). Overall survival (OS) has seldom been used as the primary end-point in contemporary phase IE RCT. Statistically significant OS has not been frequently attained in the focus study and has typically been preceded by statistically significant gains in progression-free survival (PFS). One of the greatest reasons for this is the extension of post progression survival (PPS). Increased numbers of agents have become available due to Phase IH RCT, PPS has been extended and the effects of PFS in early lines have been diluted to impact OS. In this situation, the algorithm based on such evidence from Phase IE RCT may not useful for achieving the true end-point, which is the extension of OS. Accordingly, further studies are needed to understand the role of PFS versus PPS in determining OS. The reported adverse effects (AE) of molecular targeted drugs are shown in Table 2. Molecular targeted-based agents have unique and characteristic AEs. Sequential administration is mainstream at present, however we may need to consider the AE actual usage of the agents. Conclusively, we need to integrate and develop all available knowledge in order to obtain the optimal treatment methods to extend the true end-point, which is overall survival, while maintaining the other true end-point, which is the quality of life in renal cell carcinoma patients.