Risk of treatment failure after first-line sunitinib therapy in patients with metastatic renal cell carcinoma.

Abstract

438 Background: Treatment options for metastatic renal cell carcinoma (mRCC) are rapidly evolving. Current treatment options include surgery, immunotherapy, and several targeted therapies including kinase inhibitors, mTOR inhibitors and anti-VEGF agents. The aim of this study was to inform choices and outcomes on the sequential use of targeted therapies for mRCC through the evaluation of the comparative effectiveness of common second-line targeted therapies following 1st line sunitinib treatment. Methods: A retrospective observational study using claims data was conducted. Final study subjects were mRCC patients who received everolimus, sorafenib or temsirolimus from 4/1/2008 to 2/29/2011 following 1st line sunitinib treatment. Patients were followed from the start of second-line treatment until treatment failure or last observation in the database. Treatment failure was defined as advancement to a third-line of mRCC therapy, or mortality. Results were analyzed using Cox proportional hazards model controlling for baseline clinical and demographic factors. Results: The study sample consisted of 257 mRCC patients who received everolimus (n=117), temsirolimus (n=75) and sorafenib (n=65) following 1st line sunitinib treatment. Patients had a mean age of 63 years, and 72% were male. The mean observation period from the start of second-line treatment was ∼6.4 months. Treatment failure was observed in 38.5% (20.2% advanced from 2nd to 3rd line and 18.3% died) of the study sample and 61.5% of patients were censored at last observation without any treatment failure event. Results from the Cox proportional hazards model indicated that, compared to everolimus, both sorafenib and temsirolimus patients experienced a statistically significant higher adjusted risk of treatment failure (sorafenib: HR=1.77, p=0.043; temsirolimus: HR=2.05, p=0.004). Conclusions: Following systemic treatment for mRCC with first-line sunitinib, patients on second-line targeted therapies were observed with differential risks of treatment failure, as defined by line advancement or death. The risk of treatment failure was significantly higher with sorafenib and temsirolimus as compared to everolimus.