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Ref Type Journal Article
PMID (27036973)
Authors Mahoney KM, Jacobus S, Bhatt RS, Song J, Carvo I, Cheng SC, Simpson M, Fay AP, Puzanov I, Michaelson MD, Atkins MB, McDermott DF, Signoretti S, Choueiri TK
Title Phase 2 Study of Bevacizumab and Temsirolimus After VEGFR TKI in Metastatic Renal Cell Carcinoma.
URL
Abstract Text Inhibiting VEGF and mammalian target of rapamycin (mTOR) pathways are standard treatment approaches for patients with metastatic renal cell carcinoma (mRCC). Here we report the activity and safety of the VEGF ligand inhibitor bevacizumab and the mTOR inhibitor temsirolimus combination in patients with clear cell (CC) and non-clear cell (NCC) mRCC whose disease had failed to respond to prior VEGF blockade.In this phase 2 investigator-initiated multicenter study, patients received bevacizumab and temsirolimus. The primary end point was 4-month progression-free survival (PFS) rate. Secondary end points included overall response rate, median overall survival (OS), toxicity, and correlative studies of biomarkers downstream of mTOR.Forty patients received at least 1 dose of therapy. Thirty-three (82.5%) had favorable/intermediate risk disease according to International Metastatic Renal Cell Carcinoma Database Consortium criteria, 13 (32.5%) with nccRCC histology. Nineteen (48.7%) had primary vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI)-refractory disease. The 4-month PFS rate was 65%. Overall median PFS and OS were 5.6 and 12.2 months. Median PFS and OS were 6.5 and 9.6 months in patients with primary VEGFR TKI-refractory disease, and 5.6 months and 13.1 months in patients with nccRCC. Dose reductions were needed in 80% of patients. Most frequent toxicities included fatigue, hypertension, dyslipidemia, and proteinuria. Dose discontinuation due to adverse events occurred in 27.5% of patients. Baseline tumor immunohistochemistry for phospho-S6 protein was not associated with clinical benefit.Combining bevacizumab and temsirolimus in patients previously treated with VEGFR TKI was possible but with dose reductions and treatment discontinuations. This combination resulted in modest activity, including in patients with primary VEGF-refractory disease and NCC histology.

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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
Gene 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