(CHICAGO, IL) – Second-line treatment with axitinib showed superior progression-free survival (PFS) but not overall survival (OS) compared with sorafenib in patients with metastatic renal cell carcinoma (RCC) previously treated with cytokines, according to updated results of the phase 3 AXIS trial reported at the 2012 American Society of Clinical Oncology Annual Meeting.

The AXIS trial randomized 723 patients with clear-cell metastatic RCC and disease progression after one systemic therapy to receive either axitinib 5mg twice daily (starting dose) or sorafenib 400mg twice daily. A total of 251 patients had previously received interleukin-2 (IL-2) or interferon-α (IFN-α), according to M. Dror Michaelson, MD, PhD, of the Massachusetts General Hospital Cancer Center, Boston.

As of June 3, 2011, median PFS was 12 months in the axitinib arm (n=126) vs 6.6 months in the sorafenib arm (n=125; HR 0.519; P<0.0001). Patients treated with an IL-2-containing regimen had a median PFS of 15.7 months with axitinib (n=37) vs 8.3 months with sorafenib (n=38), but the difference was not statistically significant (P=0.137). In the IFN-α alone group, median PFS was 12 months with axitinib (n=89) vs 6.5 months with sorafenib (n=87; HR 0.42; P<0.0001).

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However, median OS as of November 1, 2011, was 29.4 months in the cytokine-treated subgroup who received axitinib vs 27.8 months in those who received sorafenib—a nonsignificant difference (HR 0.813; P=0.144).

“An OS benefit with axitinib was not demonstrated, despite numerically longer median OS with axitinib compared with sorafenib,” Dr. Michaelson said. “The lack of OS benefit may be due to subsequent active treatment received by patients.”

Both treatment arms had similar adverse event profiles; those reported in >25% of cytokine-treated patients receiving axitinib vs sorafenib were diarrhea (49.2% vs 45.5%), hypertension (47.6% vs 42.3%), fatigue (35.7% vs 24.4%), dysphonia (29.4% vs 12.2%), and hand-foot syndrome (28.6% vs 57.7%), Dr. Michaelson reported, adding that, “few cytokine-treated patients (5.6%) discontinued axitinib due to toxicity.”

Dr. Michaelson and colleagues concluded that these results confirm prior phase 2 study results, which found that in patients with cytokine-refractory metastatic RCC, treatment with axitinib resulted in a median PFS of 13.7 months and a 5-year OS rate of 20.6%, which was superior to that of sorafenib in second-line mRCC and compares favorably with historical results of other agents in second-line mRCC.