Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study

JC. Yao, N. Fazio, S. Singh, R. Buzzoni, C. Carnaghi, E. Wolin, J. Tomasek, M. Raderer, H. Lahner, M. Voi, LB. Pacaud, N. Rouyrre, C. Sachs, JW. Valle, G. Delle Fave, E. Van Cutsem, M. Tesselaar, Y. Shimada, DY. Oh, J. Strosberg, MH. Kulke, ME. Pavel, . ,

. 2016 ; 387 (10022) : 968-77. [pub] 20151217

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc16009895
E-zdroje Online Plný text

NLK ProQuest Central od 1992-01-04 do Před 3 měsíci
Nursing & Allied Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health & Medicine (ProQuest) od 1992-01-04 do Před 3 měsíci
Family Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Psychology Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health Management Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Public Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci

Odkazy

PubMed 26703889
DOI 10.1016/s0140-6736(15)00817-x
Knihovny.cz E-zdroje

BACKGROUND: Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population. METHODS: In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783. FINDINGS: Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p<0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 [95% CI 0·40-1·05], one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 [9%] of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 [7%] vs 2 [2%]), infections (14 [7%] vs 0), anaemia (8 [4%] vs 1 [1%]), fatigue (7 [3%] vs 1 [1%]), and hyperglycaemia (7 [3%] vs 0). INTERPRETATION: Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract. FUNDING: Novartis Pharmaceuticals Corporation.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc16009895
003      
CZ-PrNML
005      
20160415105854.0
007      
ta
008      
160408s2016 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/S0140-6736(15)00817-X $2 doi
024    7_
$a 10.1016/S0140-6736(15)00817-X $2 doi
035    __
$a (PubMed)26703889
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Yao, James C $u University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jyao@mdanderson.org.
245    10
$a Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study / $c JC. Yao, N. Fazio, S. Singh, R. Buzzoni, C. Carnaghi, E. Wolin, J. Tomasek, M. Raderer, H. Lahner, M. Voi, LB. Pacaud, N. Rouyrre, C. Sachs, JW. Valle, G. Delle Fave, E. Van Cutsem, M. Tesselaar, Y. Shimada, DY. Oh, J. Strosberg, MH. Kulke, ME. Pavel, . ,
520    9_
$a BACKGROUND: Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population. METHODS: In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783. FINDINGS: Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p<0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 [95% CI 0·40-1·05], one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 [9%] of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 [7%] vs 2 [2%]), infections (14 [7%] vs 0), anaemia (8 [4%] vs 1 [1%]), fatigue (7 [3%] vs 1 [1%]), and hyperglycaemia (7 [3%] vs 0). INTERPRETATION: Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract. FUNDING: Novartis Pharmaceuticals Corporation.
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a protinádorové látky $x terapeutické užití $7 D000970
650    _2
$a dvojitá slepá metoda $7 D004311
650    _2
$a everolimus $x terapeutické užití $7 D000068338
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a gastrointestinální nádory $x farmakoterapie $x mortalita $7 D005770
650    _2
$a lidé $7 D006801
650    _2
$a nádory plic $x farmakoterapie $x mortalita $7 D008175
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a neuroendokrinní nádory $x farmakoterapie $x mortalita $7 D018358
650    _2
$a analýza přežití $7 D016019
650    _2
$a výsledek terapie $7 D016896
650    _2
$a mladý dospělý $7 D055815
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a randomizované kontrolované studie $7 D016449
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Fazio, Nicola $u Istituto Europeo di Oncologia, IRCCS, Milan, Italy.
700    1_
$a Singh, Simron $u Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
700    1_
$a Buzzoni, Roberto $u Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
700    1_
$a Carnaghi, Carlo $u IRCCS Istituto Clinico Humanitas, Rozzano, Italy.
700    1_
$a Wolin, Edward $u Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
700    1_
$a Tomasek, Jiri $u Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
700    1_
$a Raderer, Markus $u Univ. Klinik f. Innere Medizin I, AKH, Vienna, Austria.
700    1_
$a Lahner, Harald $u Universitaetsklinikum Essen, Zentrum f. Innere Medizin, Essen, Germany.
700    1_
$a Voi, Maurizio $u Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
700    1_
$a Pacaud, Lida Bubuteishvili $u Novartis Pharma AG, Basel, Switzerland.
700    1_
$a Rouyrre, Nicolas $u Novartis Pharma AG, Basel, Switzerland.
700    1_
$a Sachs, Carolin $u Novartis Pharma AG, Basel, Switzerland.
700    1_
$a Valle, Juan W $u Institute of Cancer Studies, University of Manchester, The Christie Hospital, Manchester, UK.
700    1_
$a Delle Fave, Gianfranco $u Azienda Ospedaliera Sant'Andrea, Università La Sapienza, Rome, Italy.
700    1_
$a Van Cutsem, Eric $u University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium.
700    1_
$a Tesselaar, Margot $u Nederlands Kanker Instituut, Antoni van Leeuwenhoek, Amsterdam, Netherlands.
700    1_
$a Shimada, Yasuhiro $u National Cancer Center Hospital, Tokyo, Japan.
700    1_
$a Oh, Do-Youn $u Seoul National University Hospital, Seoul, South Korea.
700    1_
$a Strosberg, Jonathan $u Moffitt Cancer Center, Tampa, FL, USA.
700    1_
$a Kulke, Matthew H $u Dana Farber Cancer Institute, Boston, MA, USA.
700    1_
$a Pavel, Marianne E $u Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
700    1_
$a ,
773    0_
$w MED00010161 $t Lancet (London, England) $x 1474-547X $g Roč. 387, č. 10022 (2016), s. 968-77
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26703889 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20160408 $b ABA008
991    __
$a 20160415105939 $b ABA008
999    __
$a ok $b bmc $g 1113324 $s 934263
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 387 $c 10022 $d 968-77 $e 20151217 $i 1474-547X $m Lancet $n Lancet $x MED00010161
LZP    __
$a Pubmed-20160408

Najít záznam

Citační ukazatele

Možnosti archivace