Axitinib: in advanced, treatment-experienced renal cell carcinoma

Area of Science:

• Oncology
• Pharmacology

Background:

• Vascular Endothelial Growth Factor (VEGF) receptor inhibitors are crucial in cancer therapy.
• Axitinib demonstrates potent inhibition of VEGF receptors 1-3.
• Existing treatments like sunitinib, sorafenib, and pazopanib have limitations.

Purpose of the Study:

• To evaluate the efficacy and safety of axitinib compared to sorafenib in advanced renal cell carcinoma (RCC).
• To assess axitinib's impact on progression-free survival (PFS) as the primary endpoint.
• To analyze overall survival (OS), objective response rates (ORR), and time to deterioration.

Main Methods:

• A pivotal phase III trial comparing axitinib (5 mg twice daily) with sorafenib (400 mg twice daily).
• Inclusion of patients with advanced RCC who progressed on first-line therapy.
• Assessment of PFS, OS, ORR, and time to deterioration as key outcomes.

Main Results:

• Axitinib significantly prolonged median progression-free survival compared to sorafenib.
• This PFS benefit was consistent across subgroups, including those previously treated with cytokines or sunitinib.
• Higher objective response rates and prolonged time to deterioration were observed with axitinib.
• No significant difference in median overall survival between the groups.
• Axitinib showed a numerically lower incidence of certain toxicities like palmar-plantar erythrodysaesthesia and anemia.

Conclusions:

• Axitinib is an effective second-line treatment for advanced renal cell carcinoma, offering improved progression-free survival over sorafenib.
• Axitinib demonstrates a favorable efficacy profile, including higher response rates and delayed disease progression or symptom worsening.
• The tolerability of axitinib is generally consistent with other VEGF receptor inhibitors, with some specific adverse events occurring less frequently than with sorafenib.