Axitinib for first-line metastatic renal cell carcinoma (mRCC): Overall efficacy and pharmacokinetic (PK) analyses from a randomized phase II study.

4503 Background: Axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptors with efficacy in mRCC. Due to PK and pharmacodynamic variability, some patients have sub-optimal drug exposures at the standard 5-mg twice daily (BID) dose. Prior analyses indicated higher drug exposure enhanced efficacy; thus, dose titration based on individual tolerability may optimize exposure and improve outcomes. A randomized phase II trial evaluated the efficacy and safety of axitinib dose titration from 5 mg BID to a maximum of 10 mg BID in first-line mRCC. Methods: Patients with treatment-naive mRCC received axitinib 5 mg BID for a 4-week lead-in period (cycle 1). Then, patients with 2 consecutive weeks of blood pressure (BP) ≤150/90 mmHg, no axitinib-related toxicities >grade 2, no dose reductions, and ≤2 antihypertensive medications were randomized in a double-blind fashion to axitinib 5 mg BID + dose titration with either axitinib (arm A) or placebo (arm B); those inelig...