PMID- 32654362
OWN - NLM
STAT- MEDLINE
DCOM- 20210205
LR  - 20210205
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
VI  - 126
IP  - 5
DP  - 2020 Nov
TI  - Randomised Phase II study comparing alternating cycles of sunitinib and 
      everolimus vs standard sequential administration in first-line metastatic renal 
      carcinoma (SUNRISES study).
PG  - 559-567
LID - 10.1111/bju.15165 [doi]
AB  - OBJECTIVE: To investigate the efficacy of alternating cycles of sunitinib and 
      everolimus vs standard sequential treatment of sunitinib followed by everolimus 
      in first-line metastatic renal cell carcinoma (mRCC), as alternating blockade of 
      vascular endothelial growth factor receptor (VEGFR) and mammalian target of 
      rapamycin (mTOR) pathways could potentially prevent the occurrence of resistance 
      to anti-VEGFR therapy in mRCC. PATIENTS AND METHODS: SUNRISES, a randomised 
      open-label Phase II study, investigated the efficacy of alternating cycles of 
      sunitinib and everolimus vs standard sequential treatment of sunitinib followed 
      by everolimus upon progression. Treatment-naive patients with clear-cell mRCC 
      were included. Alternating treatment consisted on 12 weeks of sunitinib, followed 
      by 12 weeks of everolimus. The primary endpoint was the progression-free survival 
      (PFS) rate at 1 year. The secondary endpoints included the median PFS, overall 
      survival (OS), response rate, and safety. RESULTS: Accrual was low due to the 
      advent of new-generation therapies, and the study was stopped prematurely. Only 
      41 patients out of the planned 102 patients were accrued, and randomised in a 2:1 
      ratio (15 patients to the control arm, 26 to the experimental arm). In all, 60.9% 
      of patients had performance status (PS) 0 and 39% PS 1; 63% had a favourable 
      prognostic risk profile, while 36% were intermediate risk. The primary endpoint 
      was not met. The 1-year PFS rate was 49.7% (experimental arm) vs 84.62% (control 
      arm; P = 0.11). There was a trend towards fewer Grade >/=3 adverse events with the 
      alternating approach (50% vs 73.3%; P = 0.14). The median OS was similar in both 
      treatment arms. The other secondary endpoints favoured the control arm. 
      CONCLUSIONS: The study failed to show any benefit of alternating cycles of 
      sunitinib and everolimus in patients with mRCC. The alternating approach using an 
      mTOR inhibitor does not seem to prevent the occurrence of resistance to VEGFR 
      blockade.
CI  - (c) 2020 The Authors BJU International (c) 2020 BJU International Published by John 
      Wiley & Sons Ltd.
FAU - Rodriguez-Vida, Alejo
AU  - Rodriguez-Vida A
AUID- ORCID: 0000-0002-7304-6857
AD  - Hospital del Mar-Institut Hospital del Mar d'Investigacions Mediques, Barcelona, 
      Spain.
FAU - Bamias, Aristotelis
AU  - Bamias A
AD  - Department of Clinical Therapeutics, Alexandra General Hospital, National and 
      Kapodistrian University of Athens, Athens, Greece.
FAU - Esteban, Emilio
AU  - Esteban E
AD  - Hospital Central de Asturias, Oviedo, Spain.
FAU - Saez, Maria Isabel
AU  - Saez MI
AD  - UGCI of Medical Oncology, Hospitales Regional and Universitario Virgen de la 
      Victoria, Malaga, Spain.
AD  - Institute of Biomedical Research (IBIMA), Malaga, Spain.
FAU - Lopez-Brea, Marta
AU  - Lopez-Brea M
AD  - Hospital Marques de Valdecilla, Santander, Spain.
FAU - Castellano, Daniel
AU  - Castellano D
AD  - Hospital 12 de Octubre, Madrid, Spain.
FAU - Caballero, Cristina
AU  - Caballero C
AD  - Hospital General Universitario de Valencia, Valencia, Spain.
FAU - Gonzalez-Larriba, Jose Luis
AU  - Gonzalez-Larriba JL
AD  - Hospital Clinico San Carlos, Madrid, Spain.
FAU - Calvo, Emiliano
AU  - Calvo E
AD  - START Madrid-CIOCC, Centro Integral Oncologico Clara Campal, Madrid, Spain.
FAU - Macia, Sonia
AU  - Macia S
AD  - Pivotal, Madrid, Spain.
FAU - Ravaud, Alain
AU  - Ravaud A
AD  - Hopital Saint Andre, Bordeaux University Hospital, Bordeaux, France.
FAU - Bellmunt, Joaquim
AU  - Bellmunt J
AUID- ORCID: 0000-0003-2328-3421
AD  - Hospital del Mar-Institut Hospital del Mar d'Investigacions Mediques, Barcelona, 
      Spain.
AD  - Beth Israel Deaconess Medical Center and PSMAR_IMIM Research Lab, Harvard Medical 
      School, Boston, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01784978
GR  - Novartis/International
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200802
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Antineoplastic Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Antineoplastic Agents/administration & dosage/adverse effects/therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/mortality/pathology
MH  - *Everolimus/administration & dosage/adverse effects/therapeutic use
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Progression-Free Survival
MH  - *Sunitinib/administration & dosage/adverse effects/therapeutic use
OTO - NOTNLM
OT  - #KidneyCancer
OT  - #kcsm
OT  - #uroonc
OT  - alternating schedules
OT  - everolimus
OT  - renal carcinoma
OT  - resistance
OT  - sunitinib
OT  - treatment sequencing
EDAT- 2020/07/13 06:00
MHDA- 2021/02/07 06:00
CRDT- 2020/07/13 06:00
PHST- 2020/07/13 06:00 [pubmed]
PHST- 2021/02/07 06:00 [medline]
PHST- 2020/07/13 06:00 [entrez]
AID - 10.1111/bju.15165 [doi]
PST - ppublish
SO  - BJU Int. 2020 Nov;126(5):559-567. doi: 10.1111/bju.15165. Epub 2020 Aug 2.