More potent vascular endothelial growth factor targeting improves progression-free survival as second-line treatment in metastatic renal cell carcinoma

Axitinib, an investigational selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 significantly extended progression-free survival (PFS) compared with sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC), according to results from an international phase 3 randomized, open-label study.

PFS was significantly longer in axitinib-treated patients who had received sunitinib or cytokines as first-line therapy, said Brian I. Rini, MD, at the Society of Clinical Oncology meeting in Chicago. Data from the study support the hypothesis that more potent biochemical targeting of the VEGF receptor improves the clinical outcome in mRCC, Dr Rini said, and axitinib "should be considered as a reference standard in the second-line treatment of advanced renal cell carcinoma." Dr Rini is associate professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and director for clinical research at the Cleveland Clinic Taussig Cancer Institute.

The trial included 723 patients with clear-cell mRCC who had progressed despite prior therapy with either sunitinib, cytokines, bevacizumab, or temsirolimus-based regimens. Patients were assigned to axitinib 5 mg twice daily or sorafenib 400 mg twice daily. Axitinib patients had their dosage titrated to 7 mg twice daily, then to 10 mg twice daily as tolerated.

Adverse events that led to discontinuation of treatment occurred in 3.9% of the axitinib group and 8.2% of the sorafenib group. Common adverse events with axitinib were hypertension, fatigue, dysphonia, and hypothyroidism.