Robert Dreicer, MD, MS, FACP

Objective response rate was higher with axitinib versus placebo titration.

Vascular epidermal growth factor (VEGF)-targeted tyrosine kinase inhibitors have become a standard of care for patients with advanced, clear-cell renal cancer. Axitinib, a potent selective inhibitor of VEGF receptors, was shown to improve progression-free survival (PFS) and objective response versus sorafenib in such patients when administered as second-line therapy (NEJM JW Oncol Hematol Nov 15 2011).

To determine whether dose titration of first-line axitinib would improve outcomes in advanced renal carcinoma, investigators conducted an industry-funded, phase II, international, randomized, double-blind study involving 213 previously untreated patients with histologically confirmed metastatic renal cell disease with a clear cell component. Patients were started on axitinib (5 mg twice daily). A total of 112 patients were then randomized to receive placebo or axitinib dose titration. Titration to a maximum dose of 10 mg twice daily was based on blood pressures of ≤150/90 mm Hg and absence of grade 3 or 4 axitinib-related toxic effects.

The objective response rate (the primary outcome) was higher with axitinib than with placebo titration (54% vs. 34%; P=0.019). At median follow-up of 26.5 months, median PFS was 14.6 months for all 213 patients; median PFS was similar with axitinib and placebo titration (hazard ratio, 0.85; P=0.24). Hypertension, hand–foot syndrome, and vomiting were ≥10% more common with axitinib titration than with placebo titration.

Citation(s):

Rini BI et al. Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: A randomised double