Clinical Developments in Renal Cell Carcinoma - Episode 4

AGILE Trial: Frontline Axitinib Versus Sorafenib in mRCC

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Several agents are available for the frontline treatment of patients with renal cell carcinoma (RCC). At this point in the conversation, panelists have explored treatment with sunitinib and pazopanib. In this segment, data is analyzed from the phase III AGILE trial that compared sorafenib to axitinib as a frontline therapy for metastatic RCC.

In the AGILE trial, 288 patients with untreated, clear cell mRCC were randomized 2:1 to receive axitinib or sorafenib, explains Thomas E. Hutson, DO, PharmD. Patient characteristics in both groups were fairly balanced, except for variations in the sorafenib arm, which had 5% more patients that had undergone nephrectomy and an additional 5% of patients with better performance status.

Leading into the trial, researchers assumed sorafenib would improve progression-free survival (PFS) by 5.5 months and axitinib by 9.8 months, or approximately a 78% improvement in PFS, notes Hutson. However, in the actual analysis, sorafenib improved PFS by 6.5 months compared to 10.1 months with axitinib (HR = 0.77; P = .38). Overall, these findings were not statistically significant and the trial did not reach its primary endpoint, says Hutson.

Despite not reaching statistical significant, the AGILE trial demonstrates that axitinib has a role in treating RCC and is a very active agent in the frontline setting. Additionally, Hutson remarks, the toxicities were similar between the two arms on the trial. Adding to this, Brian I. Rini, MD, believes this trial should remind investigators about the importance of careful clinical trial design. Furthermore, he adds, the lack of statistical significant in this trial appeared to be a direct result of the trial design and not a lack of efficacy for axitinib.