Pooled Analysis of Non-Interventional Studies of Everolimus in Patients with Metastatic Renal Cell Carcinoma (MRCC) Refractory to Anti-VEGF Therapy

ABSTRACT Background The oral mTOR inhibitor everolimus has demonstrated statistically significant PFS benefit over placebo in patients with mRCC refractory to 1 or 2 previous VEGFr-tyrosine kinase inhibitors. Here, we report prospective data on everolimus in routine clinical practice from four European countries after failure of anti-VEGF therapy. Patients and methods Data were pooled from four prospective, non-interventional studies to evaluate the safety and effectiveness of everolimus in Germany, France, Greece, and Austria. Results Data from the first 6 months of treatment of 534 patients were pooled for this analysis. At baseline, median time since diagnosis of RCC was 2.6 years and median time since diagnosis of first metastasis was 1.8 years. Most patients had predominantly clear cell mRCC (90%), had previously undergone nephrectomy (89%), and at initiation of everolimus therapy were of favourable or intermediate MSKCC risk prognosis (91%). According to investigator's assessment, 13% of patients achieved partial response and 56% of patients achieved stable disease. Overall, 77% of patients reported at least one adverse event (AE) and 22% of patients reported at least one serious AE. The most common AEs (all grades) were stomatitis (25%), anaemia (13%), asthenia (9%), fatigue (8%), pneumonitis (8%), rash (8%), diarrhoea (7%), decreased appetite (7%), hypertriglyceridaemia (6%), dyspnoea (6%), and nausea (6%). The most common serious AEs were stomatitis (3.4%), general health deterioration (2.2%), anaemia (2.1%), dyspnoea (2.1%), and pneumonitis (2.1%). A total of 24% of patients discontinued due to AEs. Percentages of patients with Karnofsky performance status ≥70 were similar at baseline (86%) and at end of this analysis (80%). Conclusions Results of this pooled analysis of European non-interventional studies of everolimus in patients with mRCC who failed previous anti-VEGF therapy confirm its safety previously reported in the pivotal multi-national RECORD-1 trial and provide preliminary information about the effectiveness of everolimus in routine use. The results support everolimus as standard of care in VEGF-refractory patients with mRCC. Disclosure L. Bergmann: Lothar Bergmann has served on advisory boards for Novartis, Pfizer, Roche, Astellas, and GlaxoSmithKline and has received honoraria from Novartis, Pfizer, Roche, and GlaxoSmithKline. L. Albiges: Laurence Albiges is consultant to Novartis and Pfizer; has received honoraria from Novartis, Bayer, and Sanofi-Aventis; and has received research funding from Novartis. M. Schmidinger: Manuela Schmidinger has received honoraria from Pfizer, GlaxoSmithKline, Novartis, Roche, and Astellas; has served as advisor for Pfizer, Roche, GlaxoSmithKline, Novartis, and Astellas; and has received research grants from Pfizer and Roche. M. Ktiouet: Meryem Ktiouet is an employee of Novartis Pharma. G. Fischer: Gregor Fischer is an employee of Novartis Pharma GmbH. D. Xanthaki: Despoina Xanthaki is an employee of Novartis (Hellas) S.A.C.I. G. Guderian: Gernot Guderian is an employee of Novartis Pharma GmbH. All other authors have declared no conflicts of interest.