PMID- 29794066
OWN - NLM
STAT- MEDLINE
DCOM- 20200324
LR  - 20200324
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 24
IP  - 1
DP  - 2019 Jan
TI  - Phase II Study of Everolimus and Octreotide LAR in Patients with Nonfunctioning 
      Gastrointestinal Neuroendocrine Tumors: The GETNE1003_EVERLAR Study.
PG  - 38-46
LID - 10.1634/theoncologist.2017-0622 [doi]
AB  - BACKGROUND: Antitumor activity of the combination of somatostatin analogues 
      (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in 
      patients with neuroendocrine tumors (NETs) has been reported but not confirmed in 
      prospective trials. MATERIALS AND METHODS: This prospective, multicenter, 
      single-arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA 
      octreotide 30 mg every 28 days in patients with advanced nonfunctioning 
      well-differentiated gastrointestinal NETs (GI-NETs) that progressed in the last 
      12 months (ClinicalTrials.gov NCT01567488). Prior treatment with SSAs and any 
      systemic or locoregional therapy was allowed except for mTOR inhibitors. Patients 
      continued treatment until disease progression or unacceptable adverse events 
      (AEs). The primary endpoint was progression-free survival (PFS) at 12 months; 
      secondary endpoints included early biochemical response, objective response rate 
      (ORR) by RECIST v1.0, overall survival (OS), AEs, activation of mTOR pathway 
      (insulin-like growth factor 1 receptor [IGF1R] and phosphoS6 [pS6] expression). 
      RESULTS: Forty-three patients were included in the intent-to-treat analyses. 
      After 12 months of treatment, 62.3% (95% confidence interval [CI] 48%-77%) of 
      patients had not progressed or died. The 24-month PFS rate was 43.6% (95% CI 
      29%-58%). The confirmed ORR was 2.3%, and stable disease was 58.1%. Median OS was 
      not reached after 24 months of median follow-up. Dose reductions and temporary 
      interruptions due to AEs were required in 14 (33%) and 33 (77%) patients, 
      respectively. The most frequent AEs were diarrhea, asthenia, mucositis, rash, and 
      hyperglycemia. No correlation was observed between IGFR1 and pS6 expression and 
      PFS/OS. CONCLUSION: The everolimus-octreotide combination provided clinically 
      relevant efficacy in nonfunctioning GI-NETs, similar to the results of RADIANT-2 
      in functioning setting. IMPLICATIONS FOR PRACTICE: The EVERLAR study reports 
      prospective data of somatostatin analogue in combination with everolimus in 
      nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful 
      activity and favorable toxicity profile that supports drug combination in this 
      setting.
CI  - (c) AlphaMed Press 2018.
FAU - Capdevila, Jaume
AU  - Capdevila J
AD  - Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, 
      Barcelona, Spain jacapdevila@vhebron.net.
FAU - Teule, Alexandre
AU  - Teule A
AD  - Catalan Institute of Oncology (ICO), Bellvitge, Barcelona, Spain.
FAU - Barriuso, Jorge
AU  - Barriuso J
AD  - La Paz University Hospital, Madrid, Spain.
FAU - Castellano, Daniel
AU  - Castellano D
AD  - 12 de Octubre University Hospital, Madrid, Spain.
FAU - Lopez, Carlos
AU  - Lopez C
AD  - Marques de Valdecilla University Hospital, Santander, Spain.
FAU - Manzano, Jose Luis
AU  - Manzano JL
AD  - Catalan Institute of Oncology (ICO), Badalona, Spain.
FAU - Alonso, Vicente
AU  - Alonso V
AD  - Miguel Servet University Hospital, Zaragoza, Spain.
FAU - Garcia-Carbonero, Rocio
AU  - Garcia-Carbonero R
AD  - 12 de Octubre University Hospital, Madrid, Spain.
FAU - Dotor, Emma
AU  - Dotor E
AD  - Consorci Sanitari Terrassa, Terrassa, Spain.
FAU - Matos, Ignacio
AU  - Matos I
AD  - Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, 
      Barcelona, Spain.
FAU - Custodio, Ana
AU  - Custodio A
AD  - La Paz University Hospital, Madrid, Spain.
FAU - Casanovas, Oriol
AU  - Casanovas O
AD  - ProCURE Research Program (IDIBELL), Catalan Institute of Oncology (ICO), 
      Barcelona, Spain.
FAU - Salazar, Ramon
AU  - Salazar R
AD  - Catalan Institute of Oncology (ICO), Bellvitge, Barcelona, Spain.
AD  - ProCURE Research Program (IDIBELL), Catalan Institute of Oncology (ICO), 
      Barcelona, Spain.
CN  - EVERLAR study investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01567488
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20180523
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 9HW64Q8G6G (Everolimus)
RN  - RWM8CCW8GP (Octreotide)
RN  - Gastro-enteropancreatic neuroendocrine tumor
SB  - IM
MH  - Aged
MH  - Everolimus/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Intestinal Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Neuroendocrine Tumors/*drug therapy/pathology
MH  - Octreotide/pharmacology/*therapeutic use
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Prospective Studies
MH  - Stomach Neoplasms/*drug therapy/pathology
PMC - PMC6324631
OTO - NOTNLM
OT  - Everolimus
OT  - Neuroendocrine tumors
OT  - Nonfunctioning
OT  - Octreotide
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2018/05/26 06:00
MHDA- 2020/03/25 06:00
PMCR- 2020/01/01
CRDT- 2018/05/26 06:00
PHST- 2017/11/28 00:00 [received]
PHST- 2018/03/23 00:00 [accepted]
PHST- 2018/05/26 06:00 [pubmed]
PHST- 2020/03/25 06:00 [medline]
PHST- 2018/05/26 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - theoncologist.2017-0622 [pii]
AID - ONCO12573 [pii]
AID - 10.1634/theoncologist.2017-0622 [doi]
PST - ppublish
SO  - Oncologist. 2019 Jan;24(1):38-46. doi: 10.1634/theoncologist.2017-0622. Epub 2018 
      May 23.