Clinical Outcome in Metastatic Renal Cell Carcinoma Patients After Failure of Initial Vascular Endothelial Growth Factor-Targeted Therapy
Received 30 November 2009; accepted 5 December 2009. published online 10 March 2010. Corrected Proof
Objectives
To characterize and evaluate the efficacy of second-line therapy in patients who had progressed on initial anti-vascular endothelial growth factor (VEGF) therapy.
Methods
Between 2005 and 2007, patients with mRCC who received second-line therapy after 1st-line VEGF-targeted therapy were identified across 7 cancer centers.
Results
A total of 645 mRCC patients received first-line VEGF-targeted therapy, of which 216 patients received second-line VEGF-targeted therapy (sunitinib, n = 93; sorafenib, n = 80; bevacizumab, n = 11; axitinib, n = 8) or mammalian target of rapamycin (mTOR)-inhibiting agents (temsirolimus, n = 21; everolimus, n = 3). On multivariate analysis, a higher baseline Karnofsky performance status score before first-line therapy predicted which patients were more likely to receive second-line therapy (P <.0001). The median time to treatment failure of second-line therapy was 4.9 months for anti-VEGF therapy and 2.5 months for mTOR inhibitors (P = .014) (HR: 0.52, CI: 0.29-0.91 and HR: 0.495, CI: 0.27-0.9 after adjusting for Memorial Sloan-Kettering Cancer Center prognostic factors and histology, respectively). Overall survival from start of second-line therapy was not significantly different (14.2 vs 10.6 months respectively; P = .38).
Conclusions
Baseline Karnofsky performance status is an independent predictor of receiving second-line targeted therapy. Patients who receive a second-line anti-VEGF drug appear to have a similar overall survival to those who receive a second-line anti-mTOR drug.
1Department of Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada
2Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
3Department of Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
4Department of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada
5Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio
6Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
7Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Ontario, Canada
Reprint requests: Daniel Y. C. Heng, M.D., M.P.H., F.R.C.P.C., Department of Oncology, Tom Baker Cancer Center, University of Calgary, 1331–29th Street NW, Calgary, Alberta, Canada T2N 4N2
Conflicts of interests: Toni K. Choueiri, Honoraria: Novartis, Abbott, GSK, Genentech, Consultant/Advisory role: Bayer, Onyx, Pfizer; Scott North, Honoraria: Pfizer, Bayer, Wyeth; Brian I. Rini, Honoraria: Wyeth, Pfizer, Genentech, Bayer, Onyx, Consultant/Advisory role: Pfizer, Onyx, Wyeth, Bayer, Genentech; Daniel Y. Heng, Honoraria: Bayer, Wyeth, Pfizer. Michael M. Vickers, Miranda Rogers, Andrew Percy, Daygen Finch, Ivan Zama, Tina Cheng, Jennifer J. Knox, Christian Kollmannsberger, and David F. McDermott had no conflicts of interest.
ABSTRACT