No Significant Correlation of Clinical Outcomes Between First- and Second-line Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma

Aim: To identify patients with metastatic renal cell carcinoma (mRCC) who received tyrosine kinase inhibitors (TKIs) in both first- and second-line settings in order to investigate the association of oncological outcomes between the two lines of therapy. Patients with Methods: The study included 76 consecutive patients with mRCC treated with second-line TKI therapy after the failure of first-line TKI therapy. The association of oncological outcomes between first-and second-line therapies was analyzed in these 76 patients. Results: In this series, the objective response rates (ORRs) to first-and second-line TKI therapies were 10.5% and 25.0%, respectively. The ORR to second-line TKI therapy was not significantly different among patients achieving a complete or partial response, stable disease and progressive disease to first-line TKI therapy (37.5%, 21.6% and 29.4%, respectively; p=0.34). The median durations of progression-free survival (PFS) with first-and second-line TKI therapies were 7.9 and 8.1 months, respectively, and there was no significant correlation between them (p=0.78). Out of the examined factors, the pre-treatment C-reactive protein level, number of metastatic sites and Memorial Sloan-Kettering Cancer Center risk classification model, but not the response to first-line TKI therapy, were independently associated with PFS on second-line TKI therapy, based on multivariate analysis. Conclusion: The clinical response to second-line TKI therapy is not dependent on that to first-line TKI therapy in patients with mRCC; therefore, it may not be necessary to switch to an alternative agent with a mechanism different from TKIs as second-line therapy, even if patients do not respond to first-line TKI therapy.