Effect of sunitinib (SU) administration on post-treatment survival in patients with metastatic renal cell carcinoma (mRCC) treated on the upfront randomized phase III trial of sunitinib or interferon alfa (IFN).

Abstract

4634 Background: Drugs targeting VEGFR are approved for, or under investigation in, cancer treatment. Animal experiments suggest such therapies may accelerate metastases (Ebos et al, Cancer Cell. 2009). We sought to address whether treatment with a VEGFR agent might accelerate tumor growth after its discontinuation. Methods: We compared the time on treatment (TOT), post-treatment survival (PTS), overall survival (OS), and tumor growth rate constants (g) of patients (pts) with mRCC randomized to either SU or IFN. We used linear regression models to evaluate associations between these measures. Results: Although reported response rate and progression free survival were better in the SU arm [Motzer et al., NEJM 2006], pts randomized to IFN had a longer PTS than pts randomized to SU (medians: 29.1 v 18.7 wks, p=.006). While acquisition of a growth-retarding immune response following IFN cannot be excluded, ≈ 60% of IFN pts eventually received SU or another VEGFR agent and this may have caused the longer PTS following IFN. That randomization to SU was not detrimental is supported by the observation that longer TOT did not reduce PTS (slope of regression line =-0.054, 95%CI -0.189,0.048) indicating increased SU exposure does not adversely impact PTS. Furthermore, tumor response defined as minimum sum of the longest diameters (LD) divided by initial sum of LD, and thus analyzed as a continuous variable, modestly correlated with TOT (Rsq=0.28, p < 0.001), but not at all with PTS (Rsq= 0.027, p=0.02). Similarly, the g calculated while pts received on-study treatment was correlated with TOT (Rsq=0. 68; p<0.0001) and OS (Rsq = 0.40; p<0.0001) but not PTS (Rsq=.008; p=.27). Conclusions: Neither the duration of SU treatment nor its anti-tumor activity, reflected in tumor response and g, had an effect on PTS. Thus, SU reduces tumor growth while administered, improves OS, and appears unlikely to alter tumor biology after treatment discontinuation. Concerns arising from animal models do not appear to apply to pts receiving SU.