Treatment of everolimus-resistant metastatic renal cell carcinoma with VEGF-targeted therapies

• Published in: British journal of cancer Vol. 105; no. 11; pp. 1635 - 1639
• Main Authors: Grünwald, V, Seidel, C, Fenner, M, Ganser, A, Busch, J, Weikert, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-11-2011; Nature Publishing Group
• Subjects: 692/699/67/1059/2326; 692/699/67/1059/602; 692/699/67/589/1588/1351; Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzenesulfonates - therapeutic use; Bevacizumab; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Disease-Free Survival; Drug Resistance; Drug Resistance, Neoplasm; Epidemiology; Everolimus; Female; Humans; Interferon; Interferons - administration & dosage; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidneys; Male; Medical research; Medical sciences; Metastasis; Middle Aged; Molecular Medicine; Molecular Targeted Therapy; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Niacinamide - analogs & derivatives; Oncology; Phenylurea Compounds; Pyridines - therapeutic use; Remission (Medicine); Retrospective Studies; Short Communication; Sirolimus - analogs & derivatives; Sirolimus - pharmacology; Treatment Failure; Treatment Outcome; Tumors; Tumors of the urinary system; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; sunitinib; refractory; everolimus; renal cell carcinoma; tyrosine kinase inhibitor; sorafenib; Antineoplastic agent; Carcinoma; Targeted therapy; Metastasis; Sunitinib; Cancerology; Grawitz tumor; Advanced stage; Protein synthesis inhibitor; Antiangiogenic agent; Protein-tyrosine kinase; Everolimus; Kidney disease; Treatment resistance; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Lactone; Malignant tumor; Macrolide; Vascular endothelium growth factor; Treatment; Sorafenib; Kidney cancer; Multikinase inhibitor; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.389

Background:
Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus.
Patients and methods:
Forty pts received sunitinib (
n
=19), sorafenib (
n
=8), dovitinib (
n
=10) or bevacizumab/interferon (
n
=3) after failure of everolimus. Median progression-free survival (PFS), overall survival (OS) and best tumour response (according to Response Evaluation Criteria In Solid Tumors) were analysed retrospectively. Kaplan–Meier, log-rank test and Cox regression analyses were used to estimate or predict OS and PFS.
Results:
Treatment of everolimus-resistant disease was associated with a PFS of 5.5 months. (range 0.4–22.3) and an objective partial remission (PR) in 4 pts (10%) and stable disease (SD) in 22 pts (55%). In univariate analyses, first-line treatment with sorafenib was the only variable to correlate with a prolonged PFS of treatment in everolimus-resistant disease (
P
=0.036). However, its significance as a predictive marker for subsequent therapy could not be verified in multivariate analyses.
Conclusions:
Vascular endothelial growth factor targeted therapy shows promising activity in everolimus-resistant metastatic renal cancer and warrants further studies.