LBA21_PR - Randomized Phase IIIB Trial of Temsirolimus and Bevacizumab Versus Interferon and Bevacizumab in Metastatic Renal Cell Carcinoma: Results from Intoract

Abstract

ABSTRACT Background Bevacizumab (BEV) + interferon alfa (IFN), as well as temsirolimus (TEM), have demonstrated clinical activity as 1st-line treatment of patients (pts) with metastatic renal cell carcinoma (mRCC). Based on initial data of combination therapy with TEM + BEV, a phase IIIb trial was undertaken. Methods This global phase IIIb, randomized, open-label, multicenter trial compared TEM + BEV and IFN + BEV as 1st-line treatment for pts with predominantly clear cell mRCC. Eligible pts, stratified by MSKCC prognostic risk and nephrectomy status, were randomized (1:1) to receive either TEM (25 mg intravenously [IV] weekly) + BEV (10 mg/kg IV every 2 weeks), or IFN (9 MU subcutaneously 3 times weekly) + BEV (10 mg/kg IV every 2 weeks). Dose reductions were allowed for TEM and IFN, but not for BEV. The study was designed to detect a 30% improvement in progression-free survival (PFS) by independent central review (primary end point) with 80% power while maintaining a significance level of 2.5% in a 1-sided stratified log-rank test. Results From April 2008 to October 2010, 791 pts were enrolled from 131 sites in 29 countries; 400 received TEM + BEV and 391 received IFN + BEV. Baseline demographics were balanced. Mean age was 58y, 70% were male, and 83% were white (Asian, 12%). At data cutoff for final analysis (April 19, 2012), 489 pts had independently assessed PFS events; 409 had died. Median PFS with TEM + BEV was 9.1 mo (95% confidence interval [CI]: 8.1, 10.2) vs 9.3 mo with IFN + BEV (95% CI: 9.0, 11.2); hazard ratio [HR] = 1.07 (95% CI: 0.89, 1.28; 1-sided P value = 0.759). Median OS was 25.8 mo (95% CI: 21.1, 30.7) for the TEM + BEV group and 25.5 mo (95% CI: 22.4, 30.8) for the IFN + BEV group; HR = 1.04 (95% CI: 0.85, 1.26; 1-sided P value = 0.638). Safety data were consistent with known profiles of these agents. In the TEM + BEV arm, pneumonitis frequency was lower than expected (1%). Grade ≥3 mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia were more common with TEM + BEV (P Conclusions TEM + BEV was not superior to IFN + BEV as 1st-line therapy for pts with clear cell mRCC. Disclosure B.I. Rini: Research funding and consulting from Pfizer Inc. J. Bellmunt: Consultancy and aboard contribution for Pfizer Inc. and Roche (compensated) J. Clancy: An employee of Pfizer during the conduct of this study, but is no longer employed by Pfizer Inc. Owns stocks of Pfizer Inc. K. Wang: Employee and owns stock of Pfizer inc. A. Niethammer: Employee and owns stock of Pfizer Inc. B. Escudier: Advisory role with Pfizer Inc. Honorarium received, compensated