Temsirolimus vs Sorafenib As Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the Intorsect Trial

ABSTRACT Background Temsirolimus (TEM) demonstrated an overall survival (OS) benefit vs interferon alfa in previously untreated patients (pts) with advanced renal cell carcinoma (RCC) and poor prognostic features. The efficacy of temsirolimus after VEGF inhibitor therapy is not known. This multicenter, randomized, open-label phase 3 trial compared the efficacy and safety of TEM vs sorafenib (SOR) in pts with metastatic RCC (mRCC) who failed prior sunitinib therapy. Methods RCC pts with disease progression after 1st-line sunitinib therapy and ECOG performance status 0 or 1 were enrolled. Eligible pts, stratified by duration of prior sunitinib therapy (≤ or >6 mo), prognostic risk, histology (clear cell or non–clear cell), and nephrectomy status, were randomized 1:1 to receive TEM 25 mg/wk intravenously or SOR 400 mg bid. Dose reductions were allowed for TEM (to 20 then 15 mg) and for SOR (to 400 mg/d then every other day). Study was powered to detect a 33% improvement in progression-free survival (PFS), the primary end point, by independent central review. Results From Sept 2007 to March 2011, 112 sites in 20 countries enrolled 512 pts; 259 received TEM and 253 received SOR. Baseline demographics were balanced. Median age was 60 y, 75% were male, and 67% were white (Asian, 17%). Histology was clear cell in 422 pts, non–clear cell in 90 pts. At data cutoff for final analysis (May 2012), 389 pts had independently assessed PFS events; 351 pts had died. Median PFS with TEM was 4.28 mo (95% confidence interval [CI]: 4.01, 5.43) and with SOR, 3.91 mo (95% CI: 2.80, 4.21); hazard ratio [HR] = 0.87 (95% CI: 0.71, 1.07; 2-sided P value = 0.1933). Median OS for the TEM group was 12.27 mo (95% CI: 10.13, 14.80); for the SOR group, 16.64 mo (95% CI: 13.55, 18.72); HR= 1.31 (95% CI: 1.05, 1.63; 2-sided P value = .0144). The most common adverse events (all grade, all cause) with TEM were rash, fatigue, diarrhea, anemia, and hyperglycemia; with SOR, they were diarrhea, rash, hand-foot syndrome, and decreased appetite. Conclusions TEM did not show superiority to SOR in the primary end point (PFS [independent]) or in the secondary end point of OS. Safety data were as expected for both agents. Further evaluation is needed to define the optimal sequence after prior sunitinib in advanced RCC pts. Disclosure This study was sponsored by Pfizer Inc. T. Hutson: Dr. Hutson is a Study Investigator for Pfizer Inc. B. Escudier: Advisory role for Aveo, Bayer, GSK, Novartis, Pfizer Inc G.A. Bjarnason: Has received honoraria for talks given, support for travel to meetings and advisory boards, and funding for investigator initiated trials from Pfizer Inc. P. Senico: Employee and stock owner of Pfizer Inc. A. Niethammer: Employee and stock owner of Pfizer Inc. D. Lu: Employee and stock owner of Pfizer Inc. S. Hariharan: Employee and stock owner of Pfizer Inc. R.J. Motzer: Research Funding and Consultancy with Pfizer Inc. All other authors have declared no conflicts of interest.