title: RECORD-2: phase II randomized study of everolimus and bevacizumab versus interferon α-2a and bevacizumab as first-line therapy in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  The open-label, phase II RECORD-2 trial compared efficacy and safety of first-line everolimus plus bevacizumab (EVE/BEV) with interferon plus bevacizumab (IFN/BEV) in patients with metastatic renal cell carcinoma.
  
  
  METHODS
  Previously untreated patients were randomized 1:1 to bevacizumab 10 mg/kg every 2 weeks with either everolimus 10 mg/day (EVE/BEV) or interferon (9 MIU 3 times/week, if tolerated) (IFN/BEV). Tumor assessments occurred every 12 weeks. The primary objective was the assessment of treatment effect on progression-free survival (PFS), based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success).
  
  
  RESULTS
  Baseline characteristics were balanced between the EVE/BEV (n = 182) and IFN/BEV (n = 183) arms. The median PFS was 9.3 and 10.0 months in the EVE/BEV and IFN/BEV arms, respectively (P = 0.485). The predicted probability of phase III success was 5.05% (hazard ratio = 0.91; 95% confidence interval 0.69-1.19). The median duration of exposure was 8.5 and 8.3 months for EVE/BEV and IFN/BEV, respectively. The percentage of patients discontinuing because of adverse events (AEs) was 23.4% for EVE/BEV and 26.9% for IFN/BEV. Common grade 3/4 AEs included proteinuria (24.4%), stomatitis (10.6%), and anemia (10.6%) for EVE/BEV and fatigue (17.1%), asthenia (14.4%), and proteinuria (10.5%) for IFN/BEV. The median overall survival was 27.1 months in both arms.
  
  
  CONCLUSIONS
  The efficacy of EVE/BEV and IFN/BEV appears similar. No new or unexpected safety findings were identified and, with the exception of proteinuria in about one-fourth of the population, EVE/BEV was generally well tolerated.
  ClinicalTrials.gov: NCT00719264.
authors: Department of Medical Oncology, Hopital Saint Andre Bordeaux University Hospital, Bordeaux, France alain.ravaud@chu-bordeaux.fr.
authors: A
authors: A
authors: Ravaud
authors: Department of Medicine, PUCRS School of Medicine, Porto Alegre, Brazil.
authors: C H
authors: CH
authors: Barrios
authors: Hertzen Cancer Research Institute, Moscow, Russia.
authors: B
authors: B
authors: Alekseev
authors: OncoCare Cancer Centre, Singapore.
authors: M-H
authors: MH
authors: Tay
authors: St Luke's University Hospital and Health Network, Bethlehem, USA.
authors: S S
authors: SS
authors: Agarwala
authors: Medical Oncology Department, Hacettepe University Institute of Oncology, Ankara, Turkey.
authors: S
authors: S
authors: Yalcin
authors: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors: C-C
authors: CC
authors: Lin
authors: Leningrad Regional Oncology Center, St Petersburg.
authors: L
authors: L
authors: Roman
authors: Russian Research Center for Radiology and Surgical Technologies, St Petersburg, Russia.
authors: M
authors: M
authors: Shkolnik
authors: Novartis Pharma AG, Basel, Switzerland.
authors: O
authors: O
authors: Anak
authors: Novartis Pharma AG, Basel, Switzerland.
authors: S
authors: S
authors: Gogov
authors: Novartis Oncology, East Hanover, USA.
authors: D
authors: D
authors: Pelov
authors: Novartis Pharma, Novartis Oncology BDM, Paris, France.
authors: A-L
authors: AL
authors: Louveau
authors: Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors: B
authors: B
authors: Melichar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: C554158:IFNA2 protein, human; D016898:Interferon-alpha; D000068258:Bevacizumab; D000068338:Everolimus
keywords: bevacizumab; combination targeted therapy; everolimus; first-line; metastatic renal cell carcinoma