Clinical factors associated with outcome in patients with metastatic clear‐cell renal cell carcinoma treated with vascular endothelial growth factor‐targeted therapy

• Published in: Cancer 2007-08, Vol.110 (3), p.543-550
• Main Authors: Choueiri, Toni K., Garcia, Jorge A., Elson, Paul, Khasawneh, Mohamad, Usman, Saif, Golshayan, Ali Reza, Baz, Rachid C., Wood, Laura, Rini, Brian I., Bukowski, Ronald M.
• Format: Article
• Language: English
• Subjects: advanced renal cell carcinoma; angiogenesis; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzenesulfonates - administration & dosage; Bevacizumab; Biological and medical sciences; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Imidazoles - administration & dosage; Indazoles - administration & dosage; Indoles - administration & dosage; Kidney Neoplasms - drug therapy; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidneys; Male; Medical sciences; Middle Aged; Neovascularization, Pathologic; Nephrology. Urinary tract diseases; Niacinamide - analogs & derivatives; Phenylurea Compounds; Prognosis; prognostic factors; prognostic model; Prospective Studies; Pyridines - administration & dosage; Pyrroles - administration & dosage; Randomized Controlled Trials as Topic; Survival Rate; Tumors; Tumors of the urinary system; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - immunology; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22827

BACKGROUND. Therapy targeted against the vascular endothelial growth factor (VEGF) pathway is a standard of care for patients with metastatic renal cell carcinoma (RCC). The identification of patients who are more likely to benefit from these agents is warranted. METHODS. In total, 120 patients with metastatic clear‐cell RCC received bevacizumab, sorafenib, sunitinib, or axitinib on 1 of 9 prospective clinical trials at the Cleveland Clinic. Clinical features associated with outcome were identified by univariate analysis; then, a stepwise modeling approach based on Cox proportional hazards regression was used to identify independent prognostic factors and to form a model for progression‐free survival (PFS). A bootstrap algorithm was used to provide internal validation. RESULTS. The overall median PFS was 13.8 months, and the objective response according to the Response Criteria in Solid Tumors was 34%. Multivariate analysis identified time from diagnosis to current treatment 300 K/μL and >4.5 K/μL, respectively; baseline corrected serum calcium 10 mg/dL; and initial Eastern Cooperative Oncology Group performance status >0 as independent, adverse prognostic factors (PF) for PFS. Three prognostic subgroups were formed based on the number of adverse prognostic factors present. The median PFS in patients with 0 or 1 adverse prognostic factor was 20.1 months compared with 13 months in patients with 2 adverse prognostic factors and 3.9 months in patients with >2 adverse prognostic factors. CONCLUSIONS. Five independent prognostic factors for predicting PFS were identified and were used to categorize patients with metastatic RCC who received VEGF‐targeted therapies into 3 risk groups. These prognostic factors can be incorporated into patient care and clinical trials that use such novel, VEGF‐targeted agents. Cancer 2007. © 2007 American Cancer Society. Clinical features that were associated with outcome were identified in 120 patients with metastatic renal cell carcinoma who received treatment with vascular endothelial growth factor (VEGF) inhibitors. Time from diagnosis to current treatment, baseline platelet and neutrophil counts, baseline corrected serum calcium level, and initial Eastern Cooperative Oncology Group performance status were found to be independent, adverse prognostic factors for progression‐free survival. These prognostic factors may be incorporated into patient care and clinical