Entry Detail
| General information | |
| Database: | DB00500 |
| Objective: | Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab or sunitinibrefractory mRCC have not been prospectively investigated. |
| Authors: | Garcia JA, et al |
| Title: | Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab. |
| Journal: | Cancer. |
| Year: | 2010 |
| PMID: | 20806321 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal carcinoma with predominant clear cell histology |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | prospectivephase II study |
| Key Patients Feature: | Eligibility criteria included histologically documentedmRCC with predominant clear cell histology, prior nephrectomy, Eastern Cooperative Oncology Group(ECOG) performance status of 0 to 1, measurable disease, and evidence of PD after treatment with either sunitinibor bevacizumab as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Patients with previously treated central nervous system(CNS) metastases were eligible, provided they had no evidence of CNS disease progression on imaging performedat least 2 weeks after definitive treatment of their CNS disease. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib |
| Primary End Point: | tumor burden reduction rate, defined as the proportion of patients with more than and equal to 5% reduction in the sum of RECISTdefined target lesions without other PD. |
| Secondary End Point: | progression free survival (PFS), duration of response, overall survival, and safety. |
| Patients Number: | 48 |
| Trial Results | |
| DLT_MTD: | Most treatmentrelatedadverse events were of mildtomoderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantarerythrodysesthesia (PPE). |
| Objective Response Rate: | 1 (2%)patient achieved an unconfirmed PR, 20 (43%) patientshad a best response of SD, 19 (40%) patients had PD, including 7 patients who developed PD before their firstrestaging scan, and 7 (15%) patients were not evaluable orhad missing data |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.4 months (95% CI, 3.65.9). |
| Median OS A vs. C: | 16.0 months (95% CI, 7.632.3). |
| Adverse Event(agent arm): | Most treatmentrelated adverse events were of mildtomoderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (P .03) and mucositis (P .06), whereas sunitinibtreated patients tended to develop more skin rash (P .06). |
| Conclusions: | Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factortargeted therapy in mRCC. |