| General information |
| Database: | DB00467 |
| Objective: | On the basis of evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxiadriven residual VEGF and other proangiogenic factors, combinations of agents from these classes were hypothesized to improve treatment outcomes relative to singleagent VEGF pathway blockade. |
| Authors: | Flaherty KT, et al |
| Title: | BEST: A Randomizedphase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell CarcinomaA Trial of the ECOGACRIN Cancer Research Group (E2804). |
| Journal: | J Clin Oncol. |
| Year: | 2015 |
| PMID: | 26077237 |
| Trial Design |
| Clinical Trial Id: | NCT00378703 |
| Agent: | bevacizumab, sorafenib
|
| Target: | NA
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced clear cell renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | B (bevacizumab 10 mg/kg IV every 2 weeks + temsirolimus 25 mg IV every week), C (bevacizumab 5 mg/kg IV every 2 weeks + sorafenib 200 mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, + 22 to 26), or D (sorafenib 200 mg twice daily + temsirolimus 25 mg IV weekly). |
| Study Type: | A Randomizedphase II Study |
| Key Patients Feature: | patients with metastatic clear cell renal cell carcinoma |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | arm A (bevacizumab monotherapy 10 mg/kg intravenously [IV] every 2 weeks), B (bevacizumab 10 mg/kg IV every 2 weeks and temsirolimus 25 mg IV every week), C (bevacizumab 5 mg/kg IV every 2 weeks and sorafenib 200 mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26), or D (sorafenib 200 mg twice daily and temsirolimus 25 mg IV weekly). |
| Treatment Info: | patients were randomly assigned equally to arm A (bevacizumab monotherapy 10 mg/kg intravenously [IV] every 2 weeks), B (bevacizumab 10 mg/kg IV every 2 weeks and temsirolimus 25 mg IV every week), C (bevacizumab 5 mg/kg IV every 2 weeks and sorafenib 200 mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26), or D (sorafenib 200 mg twice daily and temsirolimus 25 mg IV weekly). |
| Primary End Point: | progression free survival |
| Secondary End Point: | NA |
| Patients Number: | 361 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median PFS was 7.5 months for bevacizumab alone (90% CI, 5.8 to 10.8 months), 7.6 months for bevacizumab plus temsirolimus (90% CI, 6.7 to 9.2 months), 9.2 months for bevacizumab plus sorafenib (90% CI, 7.5 to 11.4 months), and 7.4 months for sorafenib plus temsirolimus (90% CI, 5.6 to 7.9 months). Hazard ratios from stratified Cox proportional hazards models were 1.01, 0.89, and 1.07 (with respective P values of .95, .49, and .68) for the three combinations, respectively, compared with bevacizumab alone |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Adverse events did not differ significantly among treatment arms. |
| Conclusions: | The activity of sorafenib, temsirolimus, and bevacizumab administered in doublet combinations did not significantly improve median progression free survival in comparison with bevacizumab monotherapy. |