Clinical outcome in metastatic renal cell carcinoma patients after failure of initial vascular endothelial growth factor-targeted therapy

Objectives: To characterize and evaluate the efficacy of second-line therapy in patients who had progressed on initial anti-vascular endothelial growth factor (VEGF) therapy.

Methods: Between 2005 and 2007, patients with mRCC who received second-line therapy after 1st-line VEGF-targeted therapy were identified across 7 cancer centers.

Results: A total of 645 mRCC patients received first-line VEGF-targeted therapy, of which 216 patients received second-line VEGF-targeted therapy (sunitinib, n = 93; sorafenib, n = 80; bevacizumab, n = 11; axitinib, n = 8) or mammalian target of rapamycin (mTOR)-inhibiting agents (temsirolimus, n = 21; everolimus, n = 3). On multivariate analysis, a higher baseline Karnofsky performance status score before first-line therapy predicted which patients were more likely to receive second-line therapy (P <.0001). The median time to treatment failure of second-line therapy was 4.9 months for anti-VEGF therapy and 2.5 months for mTOR inhibitors (P = .014) (HR: 0.52, CI: 0.29-0.91 and HR: 0.495, CI: 0.27-0.9 after adjusting for Memorial Sloan-Kettering Cancer Center prognostic factors and histology, respectively). Overall survival from start of second-line therapy was not significantly different (14.2 vs 10.6 months respectively; P = .38).

Conclusions: Baseline Karnofsky performance status is an independent predictor of receiving second-line targeted therapy. Patients who receive a second-line anti-VEGF drug appear to have a similar overall survival to those who receive a second-line anti-mTOR drug.