Effects of Tyrosine Kinase Inhibitors on Blood Pressure in Patients with Unresectable or Advanced Recurrent Renal...

Although cytokine therapy has been a common drug therapy for renal cell carcinoma for long since the 1980s, the evidence for the rationale of this therapy has been limited. Currently, 7 molecular targeted drugs(ie, sorafenib, sunitinib, axitinib, pazopanib, cabozantinib, everolimus, and temsirolimus)are available in Japan. Among these molecular targeted drugs, we clinically evaluated 5 tyrosine kinase inhibitors(ie, sorafenib, sunitinib, axitinib, pazopanib, and cabozantinib)in terms of their effects on blood pressure and the response rate by Bayes-mixed treatment comparison meta-analysis(Bayes- MTC analysis)to develop the decision-making model for the optimal treatment selection. Cabozantinib and axitinib exerted the greatest effect on blood pressure, and their probability of affecting blood pressure was 1.7 to 2 times higher than the probability of sunitinib. Among the 5 tyrosine kinase inhibitors, the effects of sunitinib and sorafenib on blood pressure were small. According to the results of clinical trials in Japan, hypertension was observed in 27.5% of patients treated with sorafenib, 51.0% with sunitinib, and 75.7% with axitinib. Our analysis also showed similar results. This study demonstrated that Bayes-MTC analysis is a useful tool enabling not only direct evaluation but also indirect evaluation.