Entry Detail
| General information | |
| Database: | DB00506 |
| Objective: | A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFNalpha) in progression free survival (primary end point) as firstline treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. |
| Authors: | Motzer RJ, et al |
| Title: | Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19487381 |
| Trial Design | |
| Clinical Trial Id: | NCT00083889 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an international, multicenter, randomized, phase III trial |
| Key Patients Feature: | The study population comprised patients 18years of age who had treatmentna ve metastatic RCC with a clear cell component. Additional eligibility criteria were previouslyreported. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A: sunitinib B: IFNalpha |
| Treatment Info: | pts were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFNalpha 9 MU subcutaneously thrice weekly. |
| Primary End Point: | progression free survival. |
| Secondary End Point: | objective response rate, overall survival, patientreported outcomes, and safety. |
| Patients Number: | 715 |
| Trial Results | |
| DLT_MTD: | Most treatmentrelated adverse events occurred more frequentlyin the sunitinib group than in the IFN group (Table 1). In bothgroups, the proportion of grade 3 or 4 adverse events and laboratoryabnormalities remained relatively low and consistent with longtermtreatment compared with those reported in the interim analysis |
| Objective Response Rate: | Median overall survival was greater in the sunitinib group than in the IFN 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 ofunstratified logrank test (P .013 per unstratified Wilcoxon test). By stratified logrank test, the HRwas 0.818 (95% CI, 0.669 to 0.999; P .049). Within the IFN group, 33% of patients receivedsunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuationfrom the trial. |
| Disease Control Rate: | 87% in sunitinib and 66% in IFN |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11 months for sunitinib compared with 5 months for IFN (P .001). |
| Median OS A vs. C: | Median overall survival was greater in the sunitinib group than in the IFN 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 logrank test (P .013 per unstratified Wilcoxon test). |
| Adverse Event(agent arm): | The most commonly reported sunitinibrelated grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and handfoot syndrome (9%). |
| Conclusions: | Sunitinib demonstrates longer overall survival compared with IFNalpha plus improvement in response and progression free survival in the firstline treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy. |