Background: Everolimus is approved for treatment of anti-vascular endothelial growth factor (VEGF)-refractory patients with metastatic renal cell carcinoma (mRCC). Clinical trials rarely mirror treatment reality. Thus, a broader evaluation of everolimus is valuable for routine use. Patients and Methods: A German multicenter non-interventional study documented mRCC patients starting everolimus after failure of initial VEGF-targeted therapy. Primary endpoint was effectiveness, defined as time to progression (TTP) according to investigator assessment (time from first dose to progression). Results: Of 382 documented patients, 196 were included in this interim analysis. In the efficacy population (n = 165), median TTP was 7.0 months (95% confidence interval (CI) 5.1-9.0). Among patients with < or ≥ 6 months of previous VEGF-targeted therapy, median TTP was 6.6 months (95% CI 3.8-not estimable) and 7.4 months (95% CI 4.6-9.6), respectively. Most common adverse events were anemia (13%) and dyspnea (14%). Physicians assessed high tolerance and documented high adherence to everolimus therapy (approximately 97%). Conclusion: In routine clinical practice, everolimus is effective, as measured by median TTP (longer than median progression-free survival in RECORD-1 trial), and well tolerated. Our results support everolimus use in anti-VEGF-refractory patients with mRCC.

Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin WG Jr: TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 2003;4:147-158.
Thomas GV, Tran C, Mellinghoff IK, Welsbie DS, Chan E, Fueger B, Czernin J, Sawyers CL: Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 2006;12:122-127.
Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A: Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116:4256-4265.
Novartis Pharmaceuticals Corporation: Afinitor® (everolimus) Tablets for Oral Administration. East Hanover, NJ, Novartis Pharmaceuticals Corporation, 2011.
National Comprehensive Cancer Network, Inc.: The NCCN Clinical Practice Guidelines in Oncology™ for Kidney Cancer V.2,2012. 2012.
Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF, Sinescu IC: EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010;58:398-406.
Novartis Europharm Limited: Afinitor Summary of Product Characteristics. West Sussex, UK, Novartis Europharm Ltd., September 2011.
Bergmann L, Kube U, Kindler M, Kopke T, Steiner G, Janssen J, Fries S, Goebell P, Jakob A, Steiner T, Staehler MD, Overkamp F, Albrecht M, Doehn C: A noninterventional study of everolimus in metastatic renal cell cancer after use of 1 VEGFr-TKI: results of a preplanned interim analysis of a prospective study. Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7,2011.
Di Lorenzo G., De Placido S, Buonerba C: Second-line treatment for renal cell cancer. Br J Cancer 2012;106:617-618.
10 Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ: Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378:1931-1939.
11 Pfizer Limited: Inlyta (1 mg film-coated tablets) Summary of Product Characteristics. Sandwich, UK, Pfizer Ltd., 2012.
Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman K, Senico P, Niethammer A, Lu D, Hariharan S, Motzer R: Temsirolimus vs. sorafenib as second line therapy in metastatic renal cell carcinoma: phase 3 results from the INTORSECT trial. Presented at 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012.
Angevin E, Lin C, Pande AU, Lopez JA, Gschwend J, Harzstark AL, Shi M, Anak O, Escudier BJ: A phase I/II study of dovitinib (TKI258), a FGFR and VEGFR inhibitor, in patients (pts) with advanced or metastatic renal cell cancer: phase I results. J Clin Oncol 2010;28(15 suppl):abstr 3057.
Blesius A, Beuselinck B, Chevreau C, Ravaud A, Rolland F, Oudard S, Escudier B: Are TKIs still active in patients treated with TKI and everolimus? Experience from 36 patients treated in France in the RECORD 1 trial. Presented at 35th Annual Congress of the European Society for Medical Oncology, Milan, Italy, October 8-12,2010.
Calvo E, Escudier B, Motzer RJ, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Ravaud A, Kim D, Panneerselvam A, Anak O, Figlin RA: Everolimus in metastatic renal cell carcinoma: subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 2012;48:333-339.
Seidel C, Fenner M, Reuter C, Merseburger AS, Ganser A, Grunwald V: Retrospective analyses of patient characteristics having predictive impact on survival under everolimus. Onkologie 2011;34:111-114.
Grunwald V, Karakiewics PI, Bavbek SE, Miller K, Machiels JP, Lee SH, Larkin J, Bono P, Rha SY, Castellano D, Blank CU, Knox JJ, Hawkins R, Anak O, Rosamilia M, Booth J, Pirotta N, Bodrogi I: An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. Eur J Cancer 2012;48:324-332.
Amato RJ, Jac J, Giessinger S, Saxena S, Willis JP: A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer 2009;115:2438-2446.
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