Risk of treatment failure after first-line tyrosine kinase inhibitors (TKI) therapy in patients with metastatic renal cell carcinoma.

Abstract

e15114 Background: Treatment for metastatic renal cell carcinoma (mRCC) includes surgery, immunotherapy, and/or targeted therapy: kinase inhibitors (including mTOR) and anti-VEGF agents. This analysis utilizes recent data to provide insight on comparative treatment effectiveness among common therapies after 1st line sunitinib or sorafenib (TKI). Methods: A retrospective observational study using claims data was conducted. Qualifying subjects were mRCC patients receiving targeted therapies from 4/1/2008 to 2/28/2010 following 1st line sunitinib or sorafenib (TKI) treatment. Following TKI treatments, 2nd line post mRCC observed therapies of interest included sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab, and pazopanib. Patients were followed from the start of 2nd-line until treatment failure or last observation in the database. Treatment failure was defined as advancement to a 3rd line of post 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 283 mRCC patients post 1st line TKI therapy. Second line treatment included: everolimus (n=81), temsirolimus (n=46), sunitinib (n=83), sorafenib (n=50), and All Others (n=23 miscellaneous regimens, generally including bevacizumab or pazopanib). Patients had a median age of 65 years, and 71% were male. The mean observation period from the start of 2nd line treatment post mRCC, was ~4.5 months. Overall treatment failure rate was 32.9% (16.6% advanced line and 16.3% died) and 67.1% of patients were censored at last observation without any treatment failure event. Compared to everolimus: temsirolimus was associated with a statistically significant, higher, adjusted risk of treatment failure (HR=2.51 p=0.008); Sorafenib trended toward a higher adjusted risk (HR=1.91, p=0.069); and sunitinib’s adjusted risk of treatment failure was statistically equivalent. Conclusions: Following treatment post mRCC with 1st line sunitinib or sorafenib (TKI), patients on 2nd line therapies were observed with differential risks of treatment failure, as defined by line advancement or death.