Reference Detail

Ref Type Journal Article
PMID (26077237)
Authors Flaherty KT, Manola JB, Pins M, McDermott DF, Atkins MB, Dutcher JJ, George DJ, Margolin KA, DiPaola RS
Title BEST: A Randomized Phase 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 Carcinoma--A Trial of the ECOG-ACRIN Cancer Research Group (E2804).
Journal Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 33
Issue 21
Date 2015 Jul 20
URL
Abstract Text On the basis of evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxia-driven residual VEGF and other proangiogenic factors, combinations of agents from these classes were hypothesized to improve treatment outcomes relative to single-agent VEGF pathway blockade.A total of 361 patients with metastatic clear cell renal cell carcinoma 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). Progression-free survival was the primary end point.Among 331 eligible treated patients, 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. Adverse events did not differ significantly among treatment arms.The activity of sorafenib, temsirolimus, and bevacizumab administered in doublet combinations did not significantly improve median progression-free survival in comparison with bevacizumab monotherapy.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown clear cell renal cell carcinoma no benefit Bevacizumab + Sorafenib Phase III Actionable In a Phase II clinical trial, treatment with the combination of Nexavar (sorafenib) and Avastin (bevacizumab) did not result in a significant improvement in progression-free survival compared to treatment with Avastin (bevacizumab) as a single agent (9.2 months vs 7.4 months) in patients with renal clear cell carcinoma (PMID: 26077237). 26077237
Unknown unknown clear cell renal cell carcinoma no benefit Sorafenib + Temsirolimus Phase II Actionable In a Phase II clinical trial, treatment with the combination of Nexavar (sorafenib) and Torisel (temsirolimus) did not prolong progression-free survival compared to treatment with Avastin (bevacizumab) monotherapy (7.4 months vs 7.5 months) in patients with renal clear cell carcinoma (PMID: 26077237). 26077237
Unknown unknown clear cell renal cell carcinoma no benefit Bevacizumab + Temsirolimus Phase II Actionable In a Phase II clinical trial, treatment with the combination of Torisel (temsirolimus) and Avastin (bevacizumab) did prolong progression-free survival compared to treatment with Avastin (bevacizumab) as a single agent (7.6 months vs 7.4 months) in patients with renal clear cell carcinoma (PMID: 26077237). 26077237