430 Background: Third-line targeted therapy efficacy in metastatic renal cell carcinoma (mRCC) is not well characterized and many funding bodies do not provide reimbursement for it. Methods: The International mRCC Database Consortium (IMDC) consists of consecutive patient series from 25 cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival. Cox proportional hazards models were used to adjust hazard ratios for confounders. Patients that stopped second-line therapy were divided into two groups: those that went onto third-line therapy and those did not. Results: 4,050 patients were treated with first-line targeted therapy, of which 2,011 (49.6%) had second-line therapy and 879 (21.7%) had third-line targeted therapy. The most common third-line therapies were everolimus 25%, sorafenib 14%, sunitinib 13%, temsirolimus 11%, pazopanib 10%, and axitinib 6%. IMDC prognostic groups at third-line therapy initiation were 6% favorable risk, 67% intermediate risk, and 27% poor risk. Overall response rate for third-line therapy was 10.5% and 50.9% had stable disease in those patients that were evaluable. Median PFS was 5.1 months (95% CI, 4.5-5.7) and median OS from third-line therapy initiation was 12.0 months (95% CI, 10.7-12.9). Patients stopping second-line therapy that move on to third-line therapy vs. those that do not receive third line therapy have a median OS from stopping second-line therapy of 13.1 vs. 2.3 mons (p<0.0001). When adjusted for second-line IMDC prognostic criteria and KPS at second-line treatment cessation, patients who do receive third-line therapy have a HR of death of 0.41 (95% CI, 0.32-0.52; p<0.0001) compared to those that do not receive third-line therapy. This may be in part due to patient selection. To further limit bias, when excluding patients that live less than 3 months after second-line therapy cessation, the adjusted HR was similar. Conclusions: Third-line targeted therapy has demonstrated activity and is prevalent in use. Further studies are required to determine appropriate sequencing.
Efficacy and safety of axitinib as third line therapy in metastatic renal cell carcinoma (mRCC): retrospective analysis