Compared with bevacizumab monotherapy, bevacizumab, sorafenib, and temsirolimus combinations did not improve progression-free survival (PFS) in advanced renal cell carcinoma (RCC), according to a report from the ECOG-ACRIN Cancer Research Group and published online this week in the Journal of Clinical Oncology.

The phase 2, four-arm study was conducted to see if combinations of vascular endothelial growth factor (VEGF) receptor inhibitors can improve treatment outcomes compared with using a single-agent.

The researchers randomly assigned 361 patients to arm A (bevacizumab), arm B (bevacizumab and temsirolimus), arm C (bevacizumab and sorafenib), and arm D (sorafenib and temsirolimus).

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The primary endpoint, median PFS, was relatively similar in arms A (PFS= 7.5 months; 90% CI: 5.8, 10.8), B (PFS= 7.6 months; 90% CI: 6.7, 9.2), C (PFS= 9.2 months; 90% CI: 7.5, 11.4), and D (PFS= 7.4 months; 90% CI: 5.6, 7.9).

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Moreover, the hazard ratios were similar in bevacizumab plus temsirolimus (HR=1.01; P=0.95), bevacizumab plus sorafenib (HR=0.89; P=0.49), and sorafenib plus temsirolimus (HR=1.07; P=0.68). Adverse events did not differ significantly among treatment arms as well.

The study suggests that doublet combinations do not significantly improve treatment outcomes compared with bevacizumab monotherapy in patients with advanced RCC. 


  1. Flaherty KT, Manola JB, Pins, M, et al. 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). J Clin Oncol. 2015. [Epub ahead of print]. doi: 10.1200/JCO.2015.60.9727.