Sunitinib therapy for patients (pts) with metastatic renal cell carcinoma (mRCC): Updated results of two phase II trials and prognostic factor analysis for survival
5095 Background: Two single-arm phase 2 trials reported a 42% objective response rate (ORR) with sunitinib as second-line therapy in mRCC pts (JAMA 2006;295:2516–24). Efficacy results were updated and an analysis of prognostic factors for survival was performed on pooled data. Methods: Eligibility criteria and treatment plan were nearly identical for both trials. Pts with mRCC who failed =1 prior cytokine-based therapy received sunitinib in repeated 6-week cycles of 50 mg/day orally for 4 weeks, followed by 2 weeks off treatment. Response was assessed by investigators according to RECIST. Pretreatment clinical and biochemical features were examined for prognostic factors by univariate and multivariate analysis (p<0.05 significance level was used in the backward stepwise selection procedure). Results: Updated efficacy data for 168 evaluable pts showed an ORR of 45% (95% CI: 39%, 54%), median progression-free survival (PFS) of 8.4 months (95% CI: 7.9, 10.7), and median overall survival (OS) of 22.3 months (95% CI: 14.8, 36.0). Twenty pts remain on treatment with sunitinib with the longest pt on the drug for >3.5 years with partial response for >3 years. The median duration of response was 11.6 months (95% CI: 9.9, 15.2), and included 1 pt with a complete response for >2 years. The proportion of pts alive at 2 years is 48%. Final prognostic factors for survival in the multivariate model were ECOG PS 0 vs. =1 (p=0.0034); time interval from diagnosis to sunitinib treatment =1 yr vs. <1 yr (p=0.0002); hemoglobin =13 vs. <13 g/dL for males and =11.5 vs. <11.5 g/dL for females (p=0.0002). Conclusions: Median survival is nearly 2 years, which compares favorably to the historical experience (12.7 months) in second-line therapy with other agents (JCO 2004;22:454–63). The influence of sunitinib therapy on patient survival is being investigated in a randomized phase 3 trial compared to interferon-a in first-line therapy for mRCC. Further study of prognostic factors to sunitinib therapy is warranted in the first-line setting. No significant financial relationships to disclose.