A phase III study comparing the vascular endothelial growth factor receptor (VEGFR) inhibitors axitinib and sorafenib (Nexavar) as second-line therapy in patients with metastatic renal cell carcinoma found that axitinib produced significantly longer progression-free survival. Published in The Lancet, the study appears to be the first reported phase III randomized trial comparing the effectiveness of one targeted agent against another in patients with renal cell carcinoma.
A total of 723 patients in 22 countries were randomly assigned to receive axitinib at 5 mg twice daily (n = 361) or sorafenib at 400 mg twice daily (n = 362). Patients who did not experience hypertension or adverse reactions to axitinib higher than grade 2 were allowed dose increases to 7 mg, and then to 10 mg, twice daily. Participants were not masked to study treatment. All patients were aged 18 years or older with confirmed renal clear cell carcinoma that progressed despite first-line therapy containing sunitinib (Sutent), bevacizumab (Avastin) plus interferon alfa, temsirolimus (Torisel), or cytokines.
Median progression-free survival was 6.7 months with axitinib compared to 4.7 months with sorafenib. In patients who had previously received cytokines, median progression-free survival rose to 12.1 months in the axitinib group and 6.5 months in the sorafenib group.
Patients received axitinib for a median duration of 6.4 months (range = 0.03–22) and sorafenib for 5.0 months (range = 0.03–20). By the data cutoff date, 61% of the axitinib treatment group and 71% of the sorafenib group had discontinued study treatment. This was primarily due to disease progression, which occurred among 160 patients in the axitinib group and 180 in the sorafenib group. The second most common reason for discontinuation was adverse events, including treatment-related adverse events in 14 (4%) of the patients treated with axitinib and 29 (8%) of the patients treated with sorafenib. The most common adverse events were diarrhea, hypertension, and fatigue in the axitinib arm, and diarrhea, palmar-plantar erythrodysesthesia, and alopecia in the sorafenib arm.
Data showing that axitinib led to a “statistically significant and clinically meaningful increase” in progression-free survival “support the hypothesis that biochemically more potent inhibition of the VEGFR, as achieved with axitinib, produces a more robust clinical effect” and “establish axitinib as a treatment option for second-line therapy of advanced renal cell carcinoma,” the investigators concluded. “An ongoing phase III trial is comparing axitinib and sorafenib in patients with metastatic renal cell cancer and no previous systemic first-line therapy or progressive disease after one previous systemic first-line regimen for metastatic disease containing sunitinib, cytokine(s), or both.”
The study was funded by Pfizer, which developed axitinib. ■
Rini BI, et al: Lancet, Nov. 4, 2011 (early release online).