Entry Detail
| General information | |
| Database: | DB00504 |
| Objective: | Before the development of targeted therapies, administration of cytokines (e.g., interleukin2, interferonalpha) was the primary systemic treatment option for advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase inhibitor, significantly prolonged progression free survival and overall survival in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a large (N = 903)phase III, doubleblind, randomised, placebocontrolled study of patients with advanced renal cell carcinoma resistant to standard therapy. |
| Authors: | Negrier S, et al |
| Title: | Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET. |
| Journal: | Med Oncol. |
| Year: | 2010 |
| PMID: | 19757215 |
| 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 cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 15 |
| Therapeutic Combination Content: | sorafenib+prior cytokine therapy |
| Study Type: | phase III TARGETdesigned |
| Key Patients Feature: | eligible patients were 18 years of age or older, had an Eastern Cooperative Oncology Group (ECOG)performance status (PS) of 0, 1, or 2, a Motzer score [19] ofintermediate or low, and a histologic or cytologic diagnosisof advanced RCC with at least 1 unidimensional measurable lesion by computed tomography (CT) or magneticresonance imaging (MRI). Inclusion criteria required 1prior systemic therapy ([30 days and 8 months fromrandomisation), which could have been treatment withcytokines, hormonal therapies, and/or antineoplasticagents, with disease progression during or following priortreatment (Response Evaluation Criteria in Solid Tumors[RECIST]), and adequate hepatic function at screening, defined as total bilirubin 1.59 the upper limit of normal(ULN), alanine aminotransferase (ALT) and aspartatetransaminase (AST) 2.59 ULN, amylase and lipase1.59 ULN, serum creatinine 2.09 ULN, prothrombintime (PT) or partial PT 1.59 ULN, and partial thromboplastin time (PTT) 1.59 ULN |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patients who were cytokinena ve (sorafenib: n = 77; placebo: n = 84) |
| Treatment Info: | This analysis of a patient subgroup from TARGET evaluated the safety and efficacy of sorafenib in patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patients who were cytokinena ve (sorafenib: n = 77; placebo: n = 84). |
| Primary End Point: | Efficacy variables included PFS, best tumour response, and clinical benefit rate. Safety variables included treatmentrelated and haematologic AEs. |
| Secondary End Point: | NA |
| Patients Number: | 903 |
| Trial Results | |
| DLT_MTD: | The most frequent drugrelated AEs in the sorafenib armwere similar in patients who were cytokinena ¡§ve and inthose who had received prior cytokine therapy, and includeddiarrhoea (27.3 vs. 39.8%), rash/desquamation (31.2vs. 39.6%), HFSR (22.1 vs. 30.2%), and fatigue (24.7 vs.24.1%). |
| Objective Response Rate: | In the prior cytokine group treated with sorafenib, 36 patients (9.6%) had a partial response (PR), 275 (73.5%)had stable disease (SD), and 48 (12.8%) had progressivedisease (PD). In the cytokinena ¡§ve group treated with sorafenib, seven patients (9.1%) had a PR, 58 (75.3%) had SD, 8 (10.4%) had PD, and one patient (1.3%) had a completeresponse (CR). Similar rates of SD (52.2 vs. 56.0%) and PD(38.3 vs. 31.0%) |
| Disease Control Rate: | 84% vs. 55% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | among patients with and without prior cytokine therapy (respectively 5.5 vs. 2.7 months; hazard ratio, 0.54; 95% confidence interval, 0.45-0.64 and 5.8 vs. 2.8 months; hazard ratio, 0.48; 95% confidence interval, 0.32-0.73). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Sorafenib was well tolerated in both subgroups (grade 3/4: 20 and 22%, respectively). |
| Conclusions: | Sorafenib was well tolerated in both subgroups (grade 34 20 and 22%, respectively). Sorafenib demonstrated a consistent, significant clinical benefit against advanced renal cell carcinoma, with a twofold improvement in progression free survival and disease control rate, with similar toxicities in patients with or without prior cytokine treatment. |