Background: There are several types of targeted therapy (TT) available to treat mRCC and data on outcomes and different sequences of therapies are required. Methods: Consecutive series of patients with mRCC treated with TT were examined. Multivariable analysis was performed when significant differences on univariable analysis were seen. Results: 2106 patients were included with a median follow-up of 36 months. 907 (43%) and 318 (15%) patients received subsequent second-line and third-line TT, respectively. Baseline characteristics of the groups below were not different except there were more patients with non-clear cell histology in the VEGF to mTOR group compared to the VEGF to VEGF group. When adjusting for the Heng et al poor risk criteria and non-clear cell histology, the hazard ratio of death for the VEGF to mTOR group vs the VEGF to VEGF group was 0.833 (95%CI 0.669-1.037, p=0.1016). When adjusting for poor risk criteria, the hazard ratio of death for the sunitinib to everolimus vs sunitinib to temsirolimus sequences was 0.774 (0.52-1.153, p=0.2086). Conclusions: The sequence of TT may not have a substantial effect on outcome but results of prospective randomized studies are awaited.

*First-line pazopanib and mTOR inhibitors, and second-line immunotherapy, axitinib and rechallenge were not analyzed as subgroups due to small numbers.