Phase III AXIS trial of axitinib versus sorafenib in metastatic renal cell carcinoma: Updated results among cytokine-treated patients.

4546 Background: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, improved progression-free survival (PFS) compared to sorafenib in patients with metastatic renal cell carcinoma (mRCC) in the phase III AXIS trial. In patients previously treated with cytokines, median PFS (mPFS) was 12.1 mo. In a prior phase II study of axitinib for cytokine-refractory mRCC, mPFS was 13.7 mo and the 5-yr overall survival (OS) rate was 20.6%. We report updated PFS and OS for cytokine-treated patients from the AXIS trial. Methods: 723 patients with clear-cell mRCC and progressive disease after 1 systemic therapy were enrolled, of whom 251 received prior interleukin-2 (IL-2) or interferon-α (IFN-α). Patients were randomized 1:1 to axitinib (5 mg twice daily [BID] starting dose) or sorafenib (400 mg BID). Results: As of Jun 3, 2011, mPFS (95% confidence interval [CI]) for cytokine-treated patients was 12.0 mo (10.1, 13.9) with axitinib (n=126) vs 6.6 mo (6.4, 8.3) with sorafenib (n=125): hazard ratio [HR] (95% CI) 0.519 (0.375, 0.720); p<0.0001. For those treated with an IL-2-containing regimen, mPFS (95% CI) was 15.7 mo (8.3, 19.4) with axitinib (n=37) vs 8.3 mo (4.7, 15.7) with sorafenib (n=38). For those treated with IFN-α alone, mPFS (95% CI) was 12.0 mo (10.0, 13.8) with axitinib (n=89) vs 6.5 mo (6.4, 8.2) with sorafenib (n=87). As of Nov 1, 2011, median OS (95% CI) in the cytokine-treated subgroup was 29.4 mo (24.5, not estimable) with axitinib vs 27.8 mo (23.1, 34.5) with sorafenib: HR (95% CI) 0.813 (0.555, 1.191); p=0.144. Adverse event (AE) profiles were similar in both arms. Few cytokine-treated patients (5.6%) discontinued axitinib due to toxicity. AEs reported in >25% of cytokine-treated patients receiving axitinib were diarrhea (49.2%), hypertension (47.6%), fatigue (35.7%), dysphonia (29.4%), and hand–foot syndrome (28.6%). Conclusions: Axitinib showed median PFS and OS of 1 and 2.5 yr, respectively, in cytokine-treated patients, confirming prior phase II study results, and was well tolerated. PFS was superior to that of sorafenib in second-line mRCC and compares favorably with historical results of other agents in second-line mRCC.