Axitinib vs. Sorafenib as Second-Line Therapy for mRCC: Results of AXIS Trial

CHICAGO—Axitinib demonstrated a significantly longer progression-free survival (PFS) and higher objective response compared with sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC), investigators Brian I. Rini, MD, of the Cleveland Clinic, and colleagues reported at the American Society of Clinical Oncology’s 2011 Annual Meeting. Axitinib is an orally available, potent, and selective inhibitor of VEGF receptors 1, 2, and 3.

Patients were eligible for the open-label, Phase 3 trial if they had a diagnosis of mRCC with a clear cell history; measurable disease per RECIST criteria; RECIST-defined progressive disease after one prior sunitinib-, bevacizumab + IFN-α-, temsirolimus, or cytokine-based regimen; and ECOG performance status 0–1.  Patients were stratified by ECOG performance status and prior therapy. A total of 723 patients were randomized 1:1 to axitinib (n=361), administered at a starting dose of 5mg twice daily, titrated to 7mg twice daily and then to 10mg twice daily as tolerated, or to sorafenib (n=362) 400mg twice daily. The primary endpoint was progression-free survival (PFS) per blinded, independent radiographic review. Secondary endpoints included overall survival, objective response rate, safety, and duration of response.

Baseline characteristics were balanced between the two arms and characteristic of a RCC population. Median age was 61 (range, 20–82); 72% male; 76% were Caucasian; and 55% had a PS of 0. Prior therapy included 54% sunitinib-, 35% cytokine-, 8% bevacizumab-, and 3% temsirolimus-based regimens. Median PFS was 6.7 months (95% CI [6.3–8.6]) for axitinib vs. 4.7 months [4.6–5.6] for sorafenib, with a HR of 0.665 (95% CI [0.544–0.812]; P<0.0001). When evaluating PFS by prior regimen, 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).

The following adverse events were reported more frequently with axitinib compared with sorafenib: hypertension (40% vs. 29%, all grades), fatigue (39% vs. 32%), dysphonia (31% vs. 14%), and hypothyroidism (19% vs. 8%). AEs reported more frequently with sorafenib compared with axitinib were hand-foot syndrome (27% vs. 51%), rash (13% vs. 32%), alopecia (4% vs. 32%), and anemia (4% vs. 12%).

Study investigators concluded that axitinib is safe and effective as second-line therapy for the treatment of mRCC compared to sorafenib. “These data support the hypothesis that more potent biochemical targeting of the VEGF receptor is associated with superior clinical activity in RCC. Axitinib should be considered as the reference standard in second-line treatment of advanced RCC,” said Dr. Rini.