IIIA.3 Targeted therapy in elderly cancer patients. Renal cell carcinoma

Abstract

Axitinib (AG-013736) is an oral, selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2 and 3. This phase II study investigated axitinib efficacy, safety and biomarkers in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (mRCC).In an open-label, multicentre study, 64 patients received an axitinib starting dose of 5 mg twice daily.Objective response rate (ORR) was 50.0% and median progression-free survival (PFS) was 11.0 months per independent review committee. Common treatment-related adverse events were hypertension (84%; 70% grade ⩾3), hand–foot syndrome (75%; 22% grade ⩾3) and diarrhoea (64%; 5% grade ⩾3). Eighteen patients (28%) developed proteinuria ⩾2 g/24 h and required dose reduction or treatment interruption/discontinuation. Proteinuria was a major cause for treatment discontinuation. Baseline urine protein levels were associated with development of proteinuria ⩾2 g/24 h (hazard ratio [HR] = 5.457, P = 0.0035 in patients with baseline proteinuria ⩾1+ versus <1+). Baseline urine protein levels correlated more strongly with axitinib-related proteinuria than other baseline renal function test values or blood pressure. Patients with greater decreases in soluble VEGFR-2 concentrations had significantly higher ORR and longer PFS than those with smaller decreases (ORR: 64.5% versus 37.5%, P = 0.045; median PFS: 12.9 months versus 9.2 months, HR = 0.42, P = 0.01).Axitinib showed significant antitumour activity and was well tolerated in Japanese mRCC patients. Baseline proteinuria and soluble VEGFR-2 levels may be key indicators of axitinib-induced proteinuria and efficacy, respectively.