Abstract
Background
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.
Patients and Methods
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.
Results
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.
Conclusion
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.
Keywords
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Article info
Publication history
Published online: February 23, 2016
Accepted:
February 14,
2016
Received in revised form:
February 8,
2016
Received:
December 3,
2015
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
