LBA21_PR - Randomized Phase IIIb Trial of Temsirolimus and Bevacizumab versus Interferon and Bevacizumab in Metastatic Renal Cell Carcinoma: Results from INTOR...

Date 01 October 2012
Event ESMO Congress 2012
Session Genitourinary tumors, renal cancer
Topics Cytotoxic agents
Renal Cell Cancer
Therapy
Biological therapy
Presenter Brian Rini
Authors B.I. Rini1, J. Bellmunt2, J. Clancy3, K. Wang4, A. Niethammer5, B. Escudier6
  • 1Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Taussig Cancer Institute, 44195 - Cleveland/US
  • 2Medical Oncology, University Hospital del Mar, 08003 - Barcelona/ES
  • 3Medical Oncology, Pfizer Inc, Cambridge/US
  • 4Statistics, Pfizer Inc., Pearl River/US
  • 5Pfizer Global Research And Development, Pfizer Oncology, La Jolla/US
  • 6Institut Gustave Roussy, FR-94805 - Roussy/FR

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 < 0.001); grade ≥3 neutropenia was more common with IFN + BEV (P < 0.001). 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