title: Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study.
abstract: BACKGROUND
  In China, there are currently no approved therapies for the treatment of metastatic renal cell carcinoma (mRCC) following progression with vascular endothelial growth factor (VEGF)-targeted agents. In the phase 3 RECORD-1 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus afforded clinical benefit with good tolerability in Western patients with mRCC whose disease had progressed despite VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. This phase 1b study was designed to further evaluate the safety and efficacy of everolimus in VEGFr-TKI-refractory Chinese patients with mRCC.
  
  
  METHODS
  An open-label, multicenter phase 1b study enrolled Chinese patients with mRCC who were intolerant to, or progressed on, previous VEGFr-TKI therapy (N = 64). Patients received everolimus 10 mg daily until objective tumor progression (according to RECIST, version 1.0), unacceptable toxicity, death, or study discontinuation for any other reason. The final data analysis cut-off date was November 30, 2011.
  
  
  RESULTS
  A total of 64 patients were included in the study. Median age was 52 years (range, 19-75 years) and 69% of patients were male. Median duration of everolimus therapy was 4.1 months (range, 0.0-16.1 months). Expected known class-effect toxicities related to mTOR inhibitor therapy were observed, including anemia (64%), hypertriglyceridemia (55%), mouth ulceration (53%), hyperglycemia (52%), hypercholesterolemia (50%), and pulmonary events (31%). Common grade 3/4 adverse events were anemia (20%), hyperglycemia (13%), increased gamma-glutamyltransferase (11%), hyponatremia (8%), dyspnea (8%), hypertriglyceridemia (6%), and lymphopenia (6%). Median PFS was 6.9 months (95% CI, 3.7-12.5 months) and the overall tumor response rate was 5% (95% CI, 1-13%). The majority of patients (61%) had stable disease as their best overall tumor response.
  
  
  CONCLUSIONS
  Safety and efficacy results were comparable to those of the RECORD-1 trial. Everolimus is generally well tolerated and provides clinical benefit to Chinese patients with anti-VEGF-refractory mRCC.
  
  
  BACKGROUND
  clinicaltrials.gov, NCT01152801.
authors.affiliation: Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Beijing 100142, China. guoj307@126.com
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Fangjian
authors.initials: F
authors.lastname: Zhou
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Annette
authors.initials: A
authors.lastname: Jappe
authors.forename: Patrick
authors.initials: P
authors.lastname: Straub
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pirotta
authors.forename: Sven
authors.initials: S
authors.lastname: Gogov
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044466:Asian People; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002681:China; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus