Everolimus for patients with metastatic renal cell carcinoma refractory to anti-VEGF therapy: results of a pooled analysis of non-interventional studies.
OBJECTIVE
To assess the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who failed one or two anti-VEGF therapies.


METHODS
Data from four prospective, non-interventional studies conducted in Germany, France, Greece and Austria were pooled for this analysis. Patients with mRCC of any histology (clear cell or non-clear cell) were included. VEGF-refractory patients received everolimus 10mg/day until disease progression or unacceptable toxicity. The primary objective was to determine everolimus efficacy as measured by time to progression (TTP; from baseline to progression).


RESULTS
The overall population comprised 632 patients; 493 patients received everolimus in the second-line setting. Most patients were of favourable/intermediate MSKCC risk (91%), had clear cell mRCC (89%), and had undergone nephrectomy (89%). Median TTP was 6.3months (95% confidence interval [CI], 5.9-6.8) for the overall population and 6.4months (95% CI, 5.8-6.9) for the second-line everolimus population. Similarly, median progression-free survival was 5.5months (95% CI, 5.0-6.1) for the overall population and 5.8months (95% CI, 5.0-6.4) for second-line everolimus population. Best tumour response (n=349) was complete or partial remission in 12% of patients and stable disease in 59% of patients. Overall population median overall survival (OS) was 11.2months (95% CI, 9.0-not reached). Commonly reported adverse events (AEs) (any grade) were stomatitis (25%), anaemia (15%) and asthenia (11%).


CONCLUSIONS
Results of this pooled analysis provide evidence of safety and effectiveness of second-line everolimus in routine clinical use and support everolimus as a standard of care for VEGF-refractory patients with mRCC.
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. Electronic address: laurence.albiges@gustaveroussy.fr.
Laurence
L
Albiges
Private Practice Urology, Chemnitz, Germany.
Ulrich
U
Kube
Institut Jean Godinot, Reims, France.
Jean-Christophe
JC
Eymard
Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.
Manuela
M
Schmidinger
Department of Clinical Therapeutics, Athens University, Medical School, Athens, Greece.
Aristotelis
A
Bamias
Novartis Pharma SAS, Paris, France.
Nadia
N
Kelkouli
Novartis Pharma GmbH, Vienna, Austria.
Bernhard
B
Mraz
Novartis Hellas S.A.C.I., Athens, Greece.
Styliani
S
Florini
Novartis Pharma GmbH, Nuremberg, Germany.
Gernot
G
Guderian
Novartis Pharma, Origgio, Italy.
Agnese
A
Cattaneo
University Hospital Frankfurt, Tumor Center Rhein-Main, Frankfurt/Main, Germany.
Lothar
L
Bergmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005060:Europe; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068338:Everolimus
Everolimus; Metastatic renal cell carcinoma; Non-interventional; Sequential targeted therapy