Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Hutson, T. E.; Tomczak, P.; Michaelson, M. D.; Bukowski, R. M.; Oudard, S.; Negrier, S.; Szczylik, C.; Pili, R.; Bjarnason, G. A.; García-del-Muro, X.; Sosman, J. A.; Solska, E.; Wilding, G.; Thompson, J. A.; Kim, S. T.; Chen, I.; Huang, X.; Figlin, R. A. |
| Article Title: | Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma |
| Abstract: | Purpose: A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods: Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results: Median overall survival was greater in the sunitinib group than in the IFN-α group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-α group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor - signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-α (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-α (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). Conclusion: Sunitinib demonstrates longer overall survival compared with IFN-α plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy. Copyright © 2009 by the American Society of Clinical Oncology. All rights reserved. |
| Keywords: | survival; adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; treatment response; aged; disease-free survival; middle aged; survival analysis; major clinical study; overall survival; clinical trial; constipation; fatigue; mortality; neutropenia; sunitinib; diarrhea; dose response; drug safety; drug withdrawal; hypertension; hypophosphatemia; side effect; alpha interferon; comparative study; disease free survival; cancer staging; follow up; follow-up studies; neoplasm staging; anorexia; metastasis; progression free survival; controlled clinical trial; anemia; leukopenia; mucosa inflammation; nausea; randomized controlled trial; stomatitis; thrombocytopenia; vomiting; proportional hazards models; myalgia; drug administration schedule; weight reduction; creatinine blood level; pathology; dose-response relationship, drug; vasculotropin inhibitor; kidney carcinoma; kidney neoplasms; abdominal pain; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; asthenia; chill; dyspnea; fever; lymphocytopenia; rash; kaplan-meiers estimate; hair color; cancer invasion; confidence interval; confidence intervals; cytokine; proportional hazards model; kidney tumor; carcinoma, renal cell; probability; multicenter study; neoplasm metastasis; peripheral edema; xerostomia; erythema; limb pain; skin discoloration; neoplasm invasiveness; alkaline phosphatase blood level; headache; phase 3 clinical trial; maximum tolerated dose; kaplan meier method; hypothyroidism; drug administration; mammalian target of rapamycin inhibitor; gastroesophageal reflux; indoles; pyrroles; amylase blood level; dyspepsia; flatulence; glossodynia; hand foot syndrome; triacylglycerol lipase blood level; administration, oral; dry skin; alopecia; indole derivative; injections, subcutaneous; epistaxis; bilirubin blood level; uric acid blood level; pyrrole derivative; mouth pain; dysgeusia; interferon-alpha; creatine kinase blood level; oral drug administration; decreased appetite; recombinant alpha2a interferon; abnormal laboratory result; heart ejection fraction; subcutaneous drug administration |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 27 |
| Issue: | 22 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2009-08-01 |
| Start Page: | 3584 |
| End Page: | 3590 |
| Language: | English |
| DOI: | 10.1200/jco.2008.20.1293 |
| PUBMED: | 19487381 |
| PROVIDER: | scopus |
| PMCID: | PMC3646307 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 358" - "Export Date: 20 April 2012" - "CODEN: JCOND" - "Source: Scopus" |
