PMID- 25851632
OWN - NLM
STAT- MEDLINE
DCOM- 20160405
LR  - 20220409
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 26
IP  - 7
DP  - 2015 Jul
TI  - RECORD-2: phase II randomized study of everolimus and bevacizumab versus 
      interferon alpha-2a and bevacizumab as first-line therapy in patients with metastatic 
      renal cell carcinoma.
PG  - 1378-84
LID - 10.1093/annonc/mdv170 [doi]
AB  - 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. PATIENTS 
      AND 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. CLINICAL TRIAL REGISTRY AND 
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00719264.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Ravaud, A
AU  - Ravaud A
AD  - Department of Medical Oncology, Hopital Saint Andre Bordeaux University Hospital, 
      Bordeaux, France alain.ravaud@chu-bordeaux.fr.
FAU - Barrios, C H
AU  - Barrios CH
AD  - Department of Medicine, PUCRS School of Medicine, Porto Alegre, Brazil.
FAU - Alekseev, B
AU  - Alekseev B
AD  - Hertzen Cancer Research Institute, Moscow, Russia.
FAU - Tay, M-H
AU  - Tay MH
AD  - OncoCare Cancer Centre, Singapore.
FAU - Agarwala, S S
AU  - Agarwala SS
AD  - St Luke's University Hospital and Health Network, Bethlehem, USA.
FAU - Yalcin, S
AU  - Yalcin S
AD  - Medical Oncology Department, Hacettepe University Institute of Oncology, Ankara, 
      Turkey.
FAU - Lin, C-C
AU  - Lin CC
AD  - Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Roman, L
AU  - Roman L
AD  - Leningrad Regional Oncology Center, St Petersburg.
FAU - Shkolnik, M
AU  - Shkolnik M
AD  - Russian Research Center for Radiology and Surgical Technologies, St Petersburg, 
      Russia.
FAU - Anak, O
AU  - Anak O
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Gogov, S
AU  - Gogov S
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Pelov, D
AU  - Pelov D
AD  - Novartis Oncology, East Hanover, USA.
FAU - Louveau, A-L
AU  - Louveau AL
AD  - Novartis Pharma, Novartis Oncology BDM, Paris, France.
FAU - Melichar, B
AU  - Melichar B
AD  - Department of Oncology, Palacky University Medical School and Teaching Hospital, 
      Olomouc, Czech Republic.
LA  - eng
SI  - ClinicalTrials.gov/NCT00719264
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150407
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (IFNA2 protein, human)
RN  - 0 (Interferon-alpha)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Bevacizumab/administration & dosage
MH  - Carcinoma, Papillary/*drug therapy/mortality/secondary
MH  - Carcinoma, Renal Cell/*drug therapy/mortality/secondary
MH  - Everolimus/administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Interferon-alpha/administration & dosage
MH  - Kidney Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Survival Rate
MH  - Young Adult
OTO - NOTNLM
OT  - bevacizumab
OT  - combination targeted therapy
OT  - everolimus
OT  - first-line
OT  - metastatic renal cell carcinoma
EDAT- 2015/04/09 06:00
MHDA- 2016/04/06 06:00
CRDT- 2015/04/09 06:00
PHST- 2014/06/18 00:00 [received]
PHST- 2015/03/22 00:00 [accepted]
PHST- 2015/04/09 06:00 [entrez]
PHST- 2015/04/09 06:00 [pubmed]
PHST- 2016/04/06 06:00 [medline]
AID - S0923-7534(19)34495-3 [pii]
AID - 10.1093/annonc/mdv170 [doi]
PST - ppublish
SO  - Ann Oncol. 2015 Jul;26(7):1378-84. doi: 10.1093/annonc/mdv170. Epub 2015 Apr 7.