PMID- 25701452
OWN - NLM
STAT- MEDLINE
DCOM- 20160513
LR  - 20240229
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 26
IP  - 6
DP  - 2015 Jun
TI  - EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line 
      therapy for advanced renal cell carcinoma.
PG  - 1118-1123
LID - S0923-7534(19)31795-8 [pii]
LID - 10.1093/annonc/mdv078 [doi]
AB  - BACKGROUND: We hypothesised that alternating inhibitors of the vascular 
      endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin 
      pathways would delay the development of resistance in advanced renal cell 
      carcinoma (aRCC). PATIENTS AND METHODS: A single-arm, two-stage, multicentre, 
      phase 2 trial to determine the activity, feasibility, and safety of 12-week 
      cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with 
      everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or 
      prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end 
      point was proportion alive and progression-free at 6 months (PFS6m). The 
      secondary end points were feasibility, tumour response, overall survival (OS), 
      and adverse events (AEs). The correlative objective was to assess biomarkers and 
      correlate with clinical outcome. RESULTS: We recruited 55 eligible participants 
      from September 2010 to August 2012. DEMOGRAPHICS: mean age 61, 71% male, 
      favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 
      80% of participants; 64% received >/=22 weeks of alternating therapy; 78% received 
      >/=22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 
      40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial 
      responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed 
      with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 
      (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were 
      consistent with those expected for each single agent. No convincing prognostic 
      biomarkers were identified. CONCLUSIONS: The EVERSUN regimen was feasible and 
      safe, but its activity did not meet pre-specified values to warrant further 
      research. This supports the current approach of continuing anti-VEGF therapy 
      until progression or prohibitive toxicity before changing treatment. AUSTRALIAN 
      NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12609000643279.
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 - Davis, I D
AU  - Davis ID
AD  - Monash University Eastern Health Clinical School, Melbourne; ANZUP Cancer Trials 
      Group, Sydney. Electronic address: ian.davis@monash.edu.
FAU - Long, A
AU  - Long A
AD  - ANZUP Cancer Trials Group, Sydney; NHMRC Clinical Trials Centre, University of 
      Sydney, Sydney; Sydney Catalyst Translational Cancer Research Centre, University 
      of Sydney, Sydney.
FAU - Yip, S
AU  - Yip S
AD  - ANZUP Cancer Trials Group, Sydney; NHMRC Clinical Trials Centre, University of 
      Sydney, Sydney; Sydney Catalyst Translational Cancer Research Centre, University 
      of Sydney, Sydney.
FAU - Espinoza, D
AU  - Espinoza D
AD  - ANZUP Cancer Trials Group, Sydney; NHMRC Clinical Trials Centre, University of 
      Sydney, Sydney; Sydney Catalyst Translational Cancer Research Centre, University 
      of Sydney, Sydney.
FAU - Thompson, J F
AU  - Thompson JF
AD  - ANZUP Cancer Trials Group, Sydney; NHMRC Clinical Trials Centre, University of 
      Sydney, Sydney.
FAU - Kichenadasse, G
AU  - Kichenadasse G
AD  - ANZUP Cancer Trials Group, Sydney; Flinders Centre for Innovation in Cancer, 
      Flinders University, Adelaide.
FAU - Harrison, M
AU  - Harrison M
AD  - ANZUP Cancer Trials Group, Sydney; Chris O'Brien Lifehouse, Royal Prince Alfred 
      Hospital, Sydney; Liverpool Hospital, Liverpool.
FAU - Lowenthal, R M
AU  - Lowenthal RM
AD  - ANZUP Cancer Trials Group, Sydney; Royal Hobart Hospital and Menzies Institute 
      for Medical Research, University of Tasmania, Hobart.
FAU - Pavlakis, N
AU  - Pavlakis N
AD  - ANZUP Cancer Trials Group, Sydney; Royal North Shore Hospital, University of 
      Sydney, Sydney.
FAU - Azad, A
AU  - Azad A
AD  - ANZUP Cancer Trials Group, Sydney; Austin Health, Melbourne.
FAU - Kannourakis, G
AU  - Kannourakis G
AD  - ANZUP Cancer Trials Group, Sydney; Ballarat Oncology & Haematology Services and 
      Fiona Elsey Cancer Research Institute, Ballarat; Federation University, Ballarat.
FAU - Steer, C
AU  - Steer C
AD  - ANZUP Cancer Trials Group, Sydney; Border Medical Oncology, Wodonga.
FAU - Goldstein, D
AU  - Goldstein D
AD  - ANZUP Cancer Trials Group, Sydney; Prince of Wales Clinical School and Prince of 
      Wales Hospital, University of New South Wales, Sydney.
FAU - Shapiro, J
AU  - Shapiro J
AD  - ANZUP Cancer Trials Group, Sydney; Cabrini Hospital, Melbourne.
FAU - Harvie, R
AU  - Harvie R
AD  - ANZUP Cancer Trials Group, Sydney; Bill Walsh Translational Cancer Research 
      Laboratories, Kolling Institute, Sydney.
FAU - Jovanovic, L
AU  - Jovanovic L
AD  - Australian Prostate Cancer Research Centre-Queensland, Institute of Health and 
      Biomedical Innovation, Queensland University of Technology, Princess Alexandra 
      Hospital, Translational Research Institute, Brisbane.
FAU - Hudson, A L
AU  - Hudson AL
AD  - Bill Walsh Translational Cancer Research Laboratories, Kolling Institute, Sydney.
FAU - Nelson, C C
AU  - Nelson CC
AD  - ANZUP Cancer Trials Group, Sydney; Australian Prostate Cancer Research 
      Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland 
      University of Technology, Princess Alexandra Hospital, Translational Research 
      Institute, Brisbane.
FAU - Stockler, M R
AU  - Stockler MR
AD  - ANZUP Cancer Trials Group, Sydney; NHMRC Clinical Trials Centre, University of 
      Sydney, Sydney; Sydney Catalyst Translational Cancer Research Centre, University 
      of Sydney, Sydney; Chris O'Brien Lifehouse, Royal Prince Alfred Hospital, Sydney; 
      Concord Cancer Centre, Concord, Australia.
FAU - Martin, A
AU  - Martin A
AD  - ANZUP Cancer Trials Group, Sydney; NHMRC Clinical Trials Centre, University of 
      Sydney, Sydney; Sydney Catalyst Translational Cancer Research Centre, University 
      of Sydney, Sydney.
LA  - eng
SI  - ANZCTR/ACTRN12609000643279
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150220
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Australia
MH  - Carcinoma, Renal Cell/*drug therapy/enzymology/mortality/pathology
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Everolimus/*administration & dosage/adverse effects
MH  - Feasibility Studies
MH  - Female
MH  - Humans
MH  - Indoles/*administration & dosage/adverse effects
MH  - Kidney Neoplasms/*drug therapy/enzymology/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Molecular Targeted Therapy
MH  - Proportional Hazards Models
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse effects
MH  - Pyrroles/*administration & dosage/adverse effects
MH  - Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors/metabolism
MH  - Risk Factors
MH  - Sunitinib
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Time Factors
MH  - Treatment Outcome
OTO - NOTNLM
OT  - angiogenesis inhibitors
OT  - clinical trial
OT  - everolimus
OT  - renal cell carcinoma
OT  - sunitinib
OT  - vascular endothelial growth factor receptors
EDAT- 2015/02/24 06:00
MHDA- 2016/05/14 06:00
CRDT- 2015/02/22 06:00
PHST- 2014/12/05 00:00 [received]
PHST- 2015/02/09 00:00 [accepted]
PHST- 2015/02/22 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
AID - S0923-7534(19)31795-8 [pii]
AID - 10.1093/annonc/mdv078 [doi]
PST - ppublish
SO  - Ann Oncol. 2015 Jun;26(6):1118-1123. doi: 10.1093/annonc/mdv078. Epub 2015 Feb 
      20.