PMID- 23187897
OWN - NLM
STAT- MEDLINE
DCOM- 20130708
LR  - 20170527
IS  - 1931-3543 (Electronic)
IS  - 0012-3692 (Linking)
VI  - 143
IP  - 4
DP  - 2013 Apr
TI  - Everolimus plus octreotide long-acting repeatable in patients with advanced lung 
      neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled 
      RADIANT-2 study.
PG  - 955-962
LID - S0012-3692(13)60204-4 [pii]
LID - 10.1378/chest.12-1108 [doi]
AB  - BACKGROUND: The incidence of neuroendocrine tumors (NETs) has increased 
      approximately fivefold since the 1980s. A similar increase in the incidence of 
      lung NETs has been reported, but therapy has not been optimized. METHODS: This 
      exploratory subanalysis evaluated the efficacy and safety of everolimus plus 
      octreotide long-acting repeatable (LAR) in a cohort of patients with low- to 
      intermediate-grade advanced lung NET from the phase 3, randomized, 
      placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. 
      The primary end point was progression-free survival (PFS). Secondary end points 
      included objective response rate, overall survival, change from baseline in 
      biomarker levels, and safety outcomes. RESULTS: Patients were randomly assigned 
      to everolimus plus octreotide LAR (n 5 33) or placebo plus octreotide LAR (n 5 
      11). Median PFS was 13.63 months in the everolimus plus octreotide LAR arm 
      compared with 5.59 months in the placebo plus octreotide LAR arm (relative risk 
      for progression: HR, 0.72; 95% CI, 0.31-1.68; P 5 .228). More patients receiving 
      everolimus plus octreotide LAR (67%) experienced minor tumor shrinkage (not 
      partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) 
      than those receiving placebo plus octreotide LAR (27%). Most frequently reported 
      adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was 
      consistent with the overall RADIANT-2 trial and the safety profile of everolimus. 
      CONCLUSIONS: This exploratory subgroup analysis of the RADIANT-2 trial indicates 
      that in patients with advanced lung NET, the addition of everolimus to octreotide 
      LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR. 
      These clinically significant observations support the continued evaluation of 
      everolimus treatment regimens in this patient population. TRIAL REGISTRY: 
      ClinicalTrials.gov; No.: NCT00412061
FAU - Fazio, Nicola
AU  - Fazio N
AD  - European Institute of Oncology, Milan, Italy. Electronic address: 
      nicola.fazio@ieo.it.
FAU - Granberg, Dan
AU  - Granberg D
AD  - Departments of Medical Sciences and Endocrine Oncology, Uppsala University, 
      Uppsala, Sweden.
FAU - Grossman, Ashley
AU  - Grossman A
AD  - Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital 
      University of Oxford, Oxford, England.
FAU - Saletan, Stephen
AU  - Saletan S
AD  - Novartis Pharmaceuticals Corp, Florham Park, NJ.
FAU - Klimovsky, Judith
AU  - Klimovsky J
AD  - Novartis Pharmaceuticals Corp, Florham Park, NJ.
FAU - Panneerselvam, Ashok
AU  - Panneerselvam A
AD  - Novartis Pharmaceuticals Corp, Florham Park, NJ.
FAU - Wolin, Edward M
AU  - Wolin EM
AD  - Cedars-Sinai Medical Center, Los Angeles, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00412061
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chest
JT  - Chest
JID - 0231335
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - RWM8CCW8GP (Octreotide)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Chest. 2013 Apr;143(4):884-6. PMID: 23546476
MH  - Aged
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Lung Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Neoplasm Grading
MH  - Neuroendocrine Tumors/*drug therapy/mortality/pathology
MH  - Octreotide/adverse effects/*therapeutic use
MH  - Sirolimus/adverse effects/*analogs & derivatives/therapeutic use
MH  - Survival Rate
MH  - Treatment Outcome
EDAT- 2012/11/29 06:00
MHDA- 2013/07/09 06:00
CRDT- 2012/11/29 06:00
PHST- 2012/11/29 06:00 [entrez]
PHST- 2012/11/29 06:00 [pubmed]
PHST- 2013/07/09 06:00 [medline]
AID - S0012-3692(13)60204-4 [pii]
AID - 10.1378/chest.12-1108 [doi]
PST - ppublish
SO  - Chest. 2013 Apr;143(4):955-962. doi: 10.1378/chest.12-1108.