Axitinib significantly extended progression free survival in patients with previously treated advanced renal cell carcinoma (RCC) in comparison with sorafenib (Nexavar ®), the current standard of care, found the Phase III AXIS 103 study. The results - announced by Pfizer ahead of the American Society of Clinical Oncology meeting in Chicago June 3-7, 2011 - represent the first head-to-head Phase 3 comparison of active targeted therapies in advanced kidney cancer.

In recent years RCC has been dominated by targeted therapy, with three VEGFR tyrosine kinase inhibitors already approved – sorafenib, sunitinib and pazopanib. Axitinib is a small molecule TKI which inhibits multiple targets including VEFFR-1, VEGFR-2. VEGFR-3, platelet derived growth factor and C KIT, with effects on tumour growth, vascular angiogenesis and metastatic progression of cancer. The approval of axitinib would provide advanced RCC patients with an additional treatment option. Although significant progress has been made in the treatment of kidney cancer, five year survival rates still remain low at about 20%.

In the global study, including centres in US, EU and Japan, 723 patients with clear-cell advanced RCC who had progressed following prior therapy with regimens containing sunitinib (54%), cytokines (35%), bevacizumab (8%) or temsirolimus (3%) were randomised to axitinib (n= 361) at a starting dose of 5mg daily) or sorafenib (n= 362) at 400mg twice daily.

Results for the prior cytokine treated subgroup showed that progression free survival was 12.1 months in axitinib treated patients versus 6.5 months in sorafenib treated patients (P<0.0001).

Results in the prior sunitinib-treated subgroup showed that progression free survival was 4.8 months in the axitinib treated group versus 3.4 months in sorafenib treated patients (P=0.0107).

In a secondary endpoint objective response rates (either complete or partial responses assessed by independent central review) were 19.4% in the axitinib group versus 9.4% in the sorafenib group (P=0.0001).

Consistent with previous analyses, axitinib demonstrated a generally manageable safety profile hypertension was 30% more likely to occur in the axitinib arm, fatigue 39% more likely, dysphonia 31% more likely and hypothyroidism 19% more likely.

"The clinically meaningful improvement in PFS seen with axitinib is even more encouraging as it was accompanied by generally manageable tolerability, an important consideration for these patients," said Dr Brian Rini, the principal investigator from Taussig Cancer Institute at Cleveland Clinic.

A phase II study, evaluating axitinib for the treatment of hepatocellular carcinoma is currently ongoing.

Article: BI Rini, B Escudier, P Tomczak, et al. Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial. J Clin Oncol 29: 2011 (suppl; abstr 4503)