CHICAGO—Sunitinib reduces tumor growth while being administered, improves overall survival (OS), and appears unlikely to alter tumor biology after treatment discontinuation according to Krastav Blagoev, MD, from the National Science Foundation, Arlington, VA, and colleagues, who presented study data at the American Society of Clinical Oncology’s 2011 Annual Meeting.
Endpoints evaluated in this randomized, multicenter, international Phase 3 trial included time on treatment (TOT), post-treatment survival (PTS), overall survival (OS), and tumor growth rate constants (g) of patients randomized to either sunitinib or interferon alfa (IFN). Dosage, study design, number of patients enrolled and evaluated and initial results were reported at an earlier time.1
Reported response rate and progression-free survival were better in patients receiving sunitinib, however those patients randomized to IFN had a longer PTS than patients randomized to sunitinib (medians: 29.1 v 18.7 wks, P<0.006). While acquisition of a growth-retarding immune response following IFN cannot be excluded, approximately 60% of IFN patients eventually received sunitinib or another VEGFR agent and this may have caused the longer PTS following IFN.
That randomization to sunitinib 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 sunitinib 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 patients received on-study treatment was correlated with TOT (Rsq=0.68; P<0.0001) and OS (Rsq=0.49; P<0.001) but not PTS (Rsq=0.003; P=0.43).
Dr. Blagoev et al concluded that the duration of sunitinib treatment and its antitumor activity, as determined by tumor response and g, had no negative effect on PTS once therapy was discontinued. Sunitinib slowed or reversed tumor growth, but once therapy was discontinued, tumor growth returned to its pretreatment rate. “Tumors with slower growth are associated with prolonged time on treatment with sunitinib. The improved rates of overall survival seen in patients with longer time on treatment are a consequence of the greater reduction in tumor growth rate,” said Dr. Blagoev.
1. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007; 11;356(2):115-24.