Medline ® Abstract for Reference 43
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).
Flaherty KT, Manola JB, Pins M, McDermott DF, Atkins MB, Dutcher JJ, George DJ, Margolin KA, DiPaola RS
J Clin Oncol. 2015;33(21):2384. Epub 2015 Jun 15.
PURPOSE: 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.
PATIENTS AND METHODS: 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 10mg/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.
RESULTS: 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.
CONCLUSION: The activity of sorafenib, temsirolimus, and bevacizumab administered in doublet combinations did not significantly improve median progression-free survival in comparison with bevacizumab monotherapy.
Keith T. Flaherty, University of Pennsylvania, Philadelphia, PA; Judith B. Manola, Dana-Farber Cancer Institute; David F. McDermott and Michael B. Atkins, Beth Israel Deaconess Medical Center, Boston, MA; Michael Pins, Advocate Lutheran General Hospital, Park Ridge, IL; Janice J. Dutcher, Montefiore Medical Center, Bronx, NY; Daniel J. George, Duke University Medical Center, Durham, NC; Kim A. Margolin, Seattle Cancer Care Alliance, University of Washington, Seattle, WA; and Robert S. DiPaola, Cancer Institute of New Jersey at Hamilton, New Brunswick, NJ. email@example.com.