No Significant PFS Benefit With Axitinib in First-Line Metastatic RCC

The second generation VEGFR inhibitor axitinib did not significantly improve progression-free survival in first-line treatment of patients with metastatic renal cell carcinoma compared with patients treated with sorafenib.

These results come from a randomized, open-label phase III trial presented earlier this year at the Genitourinary Cancers Symposium. Final results of the study were published online by Thomas E. Hutson, DO, of US Oncology Research, and colleagues in the Lancet Oncology.

The trial included 288 patients with treatment-naive metastatic renal cell carcinoma who were randomly assigned 2:1 to treatment with axitinib (n = 192) or sorafenib (n = 96). At the July 2012 cutoff date, 59% of patients had died or progressed.

No significant difference in median progression-free survival was found between those patients assigned axitinib compared with those assigned sorafenib (10.1 months vs 6.5 months; HR = 0.77; 95% CI, 0.56-1.05).

The researchers did find that median progression-free survival was longer with axitinib in patients with ECOG performance status of 0, but not in patients with performance status of 1. In addition, objective response was more frequent in patients assigned axitinib than with sorafenib.

Serious adverse events occurred in 34% of patients assigned axitinib compared with 25% of patients assigned sorafenib.

In an editorial accompanying the results, Nadia Yousaf, MD, and James Larkin, MD, of Royal Marsden Hospital, London suggested that no efficacy was seen in this patient population because the study was underpowered.

“As the authors acknowledge, the choice of sorafenib as the control can also be criticized as a so-called low bar by comparison with pazopanib or sunitinib, because sorafenib is not generally accepted as first-line standard of care,” they wrote. “Furthermore, in calculation of sample size requirements, the benefit of sorafenib might have been underestimated because earlier studies reported a median progression-free survival of roughly 5 months.”

They went on to point out that although a study with a larger sample size might show a significant benefit for axitinib that with multiple other drugs currently being used for renal cell carcinoma, there are more pressing research issues such as “the optimum scheduling strategies of drugs already approved and expediting of the investigation of truly novel drugs such as those targeting the PD1 receptor, a molecule involved in immune checkpoint signaling.”

Axitinib is currently approved for use in second-line treatment of metastatic renal cell carcinoma.