Axitinib second-line therapy for metastatic renal cell carcinoma (mRCC): Five-year (yr) overall survival (OS) data from a phase II trial.

4547 Background: Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3. Axitinib in patients (pts) with cytokine-refractory mRCC (Rixe et al, Lancet Oncol 2007:975) showed an objective response rate (ORR) of 44%, median progression-free survival of 13.7 months, and median overall survival (OS) of 29.9 months (N=52). Updated 5-yr OS data is presented. Methods: Between 10/2003 and 4/2004, 52 pts were enrolled. Pts had histologically confirmed mRCC, measurable disease, Eastern Cooperative Oncology Group performance status (PS) of 0/1, and had failed a prior IL-2/interferon regimen. Starting axitinib doses were 5 mg twice daily; samples were obtained for peak/trough axitinib plasma levels. In 2/2007, 24 of 52 enrolled pts were alive (censored), and 11 pts continued to receive long-term axitinib in a second study. The updated OS data were collected through a third study to estimate the 5-yr survival rate of the originally enrolled 52 pts. Death dates or recent known-alive dates were available for 50 pts. Results: Of the 52 pts, 35 died of progressive disease, 5 died of “unknown causes,” 10 were alive, and 2 were lost to follow-up. Median follow-up for OS was 5.9 yrs. The 5-yr survival rate was 20.6% (95% CI, 10.9–32.4%). Treatment-emergent, all-causality grade ≥3 adverse events for the 52 pts included diarrhea (19%), fatigue (19%), hypertension (17%), weight loss (8%), and dehydration, myocardial infarction, and stomatitis (6% each). Hypothyroidism (all grades) was observed in 23%. Comparing the characteristics of the 5-yr survivors (n = 10) vs <5-yr survivors (n = 40), the former had higher ORR (100% vs 30%), longer axitinib therapy duration (median 5.8 yr vs 0.67 yr), and better baseline PS (80% vs 53% with PS 0) but were of similar median age (57 vs 60), gender (80% vs 75% males), and risk factors (50% vs 40% with zero MSKCC factors). The cycle 1 day 1 peak concentrations for the 5-year survivors appeared to have a narrower distribution (range, 23–69 ng/mL) compared with the <5-yr survivors (range, 7–147 ng/mL). Conclusions: Axitinib can produce greater than 5-yr OS in selected pts with mRCC. No new toxicities emerged with long-term axitinib therapy.