Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial.

4503 Background: Axitinib is an oral, potent, and selective inhibitor of VEGF receptors 1, 2, and 3. This randomized, open-label, phase III trial compared the efficacy and safety of axitinib versus (vs) sorafenib as second-line therapy for mRCC. Methods: Eligible patients had clear-cell mRCC; measurable, RECIST-defined progressive disease after 1 prior first-line systemic therapy with a sunitinib-, bevacizumab-, temsirolimus-, or cytokine-based regimen; and Eastern Cooperative Oncology Group performance status (PS) of 0 or 1. Patients were stratified by PS and prior therapy, then randomized 1:1 to axitinib, administered at a starting dose of 5 mg BID, titrated to 7 mg BID and then to 10 mg BID as tolerated, or sorafenib 400 mg BID. The primary endpoint was progression-free survival (PFS) per blinded, independent radiographic review. The study had 90% power to detect a PFS of 7 months vs 5 months, corresponding to a hazard ratio (HR) of ≤0.714 (overall 1-sided α=0.025). Results: Seven-hundred twenty-three patients were randomized to either axitinib (n=361) or sorafenib (n=362). Baseline patient characteristics included median age of 61; 72% male; 76% Caucasian; and 55% PS 0. Prior therapy included 54% sunitinib-, 35% cytokine-, 8% bevacizumab-, and 3% temsirolimus-based regimens. Median PFS was 6.7 months (95% confidence interval, 6.3-8.6) for axitinib vs 4.7 months (4.6-5.6) for sorafenib, with a HR of 0.665 (P<0.0001). PFS favored axitinib in both the prior cytokine subgroup (12.1 vs 6.5 months; P<0.0001) and the prior sunitinib subgroup (4.8 vs 3.4 months; P=0.0107). Objective response rates were 19.4% for axitinib vs 9.4% for sorafenib (P=0.0001). Common AEs more frequent with axitinib vs sorafenib were hypertension (40% vs 29%, all grades), fatigue (39% vs 32%), dysphonia (31% vs 14%), and hypothyroidism (19% vs 8%). AEs more frequent with sorafenib were hand-foot syndrome (27% vs 51%), rash (13% vs 32%), alopecia (4% vs 32%), and anemia (4% vs 12%). Conclusions: Axitinib demonstrated a significantly longer PFS and higher objective response rate vs sorafenib with an acceptable safety profile as second-line therapy for mRCC.