ASCO GU: Axitinib Fails to Meet Endpoint vs Sorafenib for First-Line RCC Therapy

February 19, 2013

A trial comparing axitinib to sorafenib as first-line therapy for metastatic renal cell carcinoma showed a statistically significant improvement in progression-free survival for the drug; however, the difference failed to meet the phase III trial’s prespecified significance level of 0.025.

ORLANDO, Fla.-A trial comparing axitinib (Inlyta) to sorafenib as first-line therapy for metastatic renal cell carcinoma showed an improvement in progression-free survival for the drug; however, the difference failed to meet the phase III trial’s prespecified significance level of P = .025.

Thomas E. Hutson, DO, PharmD, of Baylor Charles A. Sammons Cancer Center and US Oncology Research, Dallas, Texas, and colleagues powered the study to detect a 78% improvement in progression-free survival with a hazard ratio (HR) of 0.561. Patients assigned to 5 mg axitinib twice daily had a median progression-free survival of 10.1 months compared with 6.5 months for patients assigned to sorafenib (P = .0377; HR = 0.767; 95% confidence interval, 0.559–1.482).

Results of the trial, which was sponsored by Pfizer, were presented Saturday at the American Society of Clinical Oncology (ASCO) 2013 Genitourinary Cancers Symposium. Pfizer issued an announcement in October that the study had failed to meet its primary endpoint.

Axitinib is highly specific VEGF receptor inhibitor that has received regulatory approval in the United States for advanced renal cell cancer after failure of one prior systemic therapy. The drug was approved based on the results of the phase III AXIS trial, which showed that treatment with axitinib resulted in a 33.5% improvement in progression-free survival compared with sorafenib in patients whose disease had progressed despite treatment with prior therapy.

“In this trial of first-line therapy, axitinib has demonstrated a 3.6-month improvement in median [progression-free survival] vs sorafenib, a significantly higher response rate and an acceptable safety profile,” Hutson said. “Progression-free survival differences favoring axitinib were also observed in the prespecified performance status groups.”

When looking at the prespecified stratification of patients by ECOG performance status, those patients with performance status 0 performed well on axitinib. The median progression-free survival was 13.7 months in these patients vs 6.6 months in patients assigned sorafenib (HR = 0.64; P = .022). In addition, patients with prior nephrectomy also fared better on axitinib with a median progression-free survival of 10.3 months vs 6.4 months for patients on sorafenib (HR = 0.67; P = .009).

However, in the subset of patients with ECOG performance status of 1, median progression-free survival with axitinib was not significantly improved (6.5 months vs 6.4 months; HR = 0.93; P = .38).

Thirty-two percent of patients on axitinib had RECIST defined partial response, which, when added to stable disease, yielded a clinical benefit rate of 75%, Hutson said. With sorafenib, RECIST defined partial response was seen in 14.6% with a corresponding clinical benefit rate of 67%.

Adverse events seen were similar to those previously reported with both drugs. In this trial, hypertension (49% vs 29%) and diarrhea (50% vs 40%) were notably more frequent with axitinib, where as hand-foot syndrome was more common with sorafenib (26% vs 39%).

Hutson said that next steps will include waiting for the overall survival data from the phase III trial and exploring combinations with novel agents.

In October, Brian I. Rini, MD, of Cleveland Clinic Taussig Cancer Center, said that it was too early to put the results of this trial in perspective.

During a poster presentation at the meeting, Rini updated results of a phase II trial of axitinib with or without dose titration as front-line treatment for renal cancer. Patients were assigned to 4 weeks of axitinib 5 mg twice a day and the eligible patients were randomly assigned to placebo or axitinib 5 mg plus dose titration to 10 mg maximum. Patients who were not eligible for randomization continued on 5 mg axitinib or lower.

Median progression-free survival of patients assigned to dose titration was 14.5 months compared with 15.7 months in the placebo arm and 16.6 months in patients who were not randomized. Overall response rate was 54% in the titration arm vs 34% in the placebo arm and 59% in the nonrandomized arm.