PMID- 30105951
OWN - NLM
STAT- MEDLINE
DCOM- 20190503
LR  - 20191210
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Linking)
VI  - 28
IP  - 9
DP  - 2018 Sep
TI  - Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and 
      Poorly Differentiated Thyroid Cancer.
PG  - 1174-1179
LID - 10.1089/thy.2017.0663 [doi]
AB  - BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is 
      frequent in advanced follicular (FTC) and poorly differentiated thyroid (PDTC) 
      carcinomas and has been implicated in oncogenesis and tumor progression. This 
      study investigated the efficacy and safety of buparlisib, a pan-PI3K inhibitor in 
      radioiodine refractory FTC and PDTC. METHODS: The primary endpoint of this 
      open-label, multicenter, phase 2 pilot study was progression-free survival (PFS) 
      at 6 months. The sample size was determined considering that a PFS </=50% at 6 
      months would denote an absence of benefits (null hypothesis). Secondary endpoints 
      were objective response rate, PFS at 12 months, overall survival at 6 and 12 
      months, and safety based on the frequency and severity of adverse events (AEs). 
      RESULTS: Forty-three patients (19M/24 F; median age: 67 years) with metastatic, 
      radioiodine refractory, progressive disease received buparlisib, 100 mg, daily. 
      Histology was PDTC in 25 (58%), FTC in 17 (40%), and Hurthle cell carcinoma in 1 
      (2%). RAS mutation was found in 44% (12/27) and activation of the PI3K pathway in 
      35% (8/23) of tested tumors. The probability of PFS was 41.7% [95% confidence 
      interval (CI) 7.7-55.5] at 6 months and 20.9% [CI 0-35.7] at 12 months, lower 
      than the 50% expected PFS. At 6 months, 25.6% patients had stable disease, 48.8% 
      were progressive and 25.6% had stopped treatment due to AE. The response to 
      therapy was not influenced by age, sex, histology, or genetic alterations. The 
      overall survivals at 6 and 12 months were 85.9% [CI 76-97] and 78.7 % [CI 67-92], 
      respectively. The mean tumor growth rate decreased from 3.78 mm/month [CI 
      2.61-4.95] before treatment to 0.8 mm/month [CI -0.2-1.88] during treatment 
      (p < 0.02). Severe grade 3-4 AEs occurred in 27 patients (63%), including 
      hepatitis (25%), hyperglycemia (21%), mood disorders (12%), and skin toxicity 
      (12%), with favorable outcome after temporary or permanent treatment 
      discontinuation or dose reduction. CONCLUSIONS: Buparlisib did not result in 
      significant efficacy in advanced FTC and PDTC. However, the decrease in tumor 
      growth rate may suggest incomplete inhibition of oncogenic pathways and/or escape 
      mechanisms. This should lead to evaluate combined therapy associating inhibitors 
      of both the PI3K and mitogen-activated protein kinase pathways.
FAU - Borson-Chazot, Francoise
AU  - Borson-Chazot F
AD  - 1 Federation d'Endocrinologie, Hospices Civils de Lyon, Universite Claude Bernard 
      Lyon 1 , Lyon, France .
FAU - Dantony, Emmanuelle
AU  - Dantony E
AD  - 2 Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, Universite 
      Lyon 1 , Laboratoire de Biometrie et Biologie Evolutive, Equipe 
      Biostatistique-Sante, Villeurbanne, France .
FAU - Illouz, Frederic
AU  - Illouz F
AD  - 3 Service d'Endocrinologie, Centre de Reference de la Thyroide et des Recepteurs 
      Hormonaux , Centre Hospitalier Universitaire d'Angers, France .
FAU - Lopez, Jonathan
AU  - Lopez J
AD  - 4 Service de Biochimie et Biologie moleculaire, Centre Hospitalier Lyon-Sud , 
      Hospices Civils de Lyon, Universite Lyon 1, France .
FAU - Niccoli, Patricia
AU  - Niccoli P
AD  - 5 Departement d'Oncologie Medicale, Institut Paoli Calmette , Marseille, France .
FAU - Wassermann, Johanna
AU  - Wassermann J
AD  - 6 Departement d'oncologie Medicale, Hopital Pitie Salpetriere, Assistance 
      Publique-Hopitaux de Paris, Universite Sorbonne , Paris, France .
FAU - Do Cao, Christine
AU  - Do Cao C
AD  - 7 Service d'Endocrinologie, Centre Hospitalier Regional et Universitaire Lille , 
      France .
FAU - Leboulleux, Sophie
AU  - Leboulleux S
AD  - 8 Service de Medecine Nucleaire et de Cancerologie Endocrinienne, Institut 
      Gustave Roussy , Villejuif et Universite Paris Saclay, France .
FAU - Klein, Marc
AU  - Klein M
AD  - 9 Service d'Endocrinologie, Centre Hospitalier Universitaire et Universite de 
      Nancy , France .
FAU - Tabarin, Antoine
AU  - Tabarin A
AD  - 10 Service d'Endocrinologie, Centre Hospitalier Universitaire et Universite de 
      Bordeaux , France .
FAU - Eberle, Marie-Claude
AU  - Eberle MC
AD  - 11 Service de Medecine Nucleaire, Institut du Cancer de Montpellier , France .
FAU - Benisvy, Danielle
AU  - Benisvy D
AD  - 12 Service de Medecine Nucleaire, Centre Antoine Lacassagne , Nice, France .
FAU - de la Fouchardiere, Christelle
AU  - de la Fouchardiere C
AD  - 13 Departement d'Oncologie Medicale, Centre Leon Berard , Lyon, France .
FAU - Bournaud, Claire
AU  - Bournaud C
AD  - 14 Centre de Medecine Nucleaire, Groupement Hospitalier Est , Hospices Civils de 
      Lyon, France .
FAU - Lasolle, Helene
AU  - Lasolle H
AD  - 1 Federation d'Endocrinologie, Hospices Civils de Lyon, Universite Claude Bernard 
      Lyon 1 , Lyon, France .
FAU - Delahaye, Armelle
AU  - Delahaye A
AD  - 1 Federation d'Endocrinologie, Hospices Civils de Lyon, Universite Claude Bernard 
      Lyon 1 , Lyon, France .
FAU - Rabilloud, Muriel
AU  - Rabilloud M
AD  - 2 Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, Universite 
      Lyon 1 , Laboratoire de Biometrie et Biologie Evolutive, Equipe 
      Biostatistique-Sante, Villeurbanne, France .
FAU - Lapras, Veronique
AU  - Lapras V
AD  - 15 Service de Radiologie, Centre Hospitalier Lyon-Sud , Hospices Civils de Lyon, 
      France .
FAU - Decaussin-Petrucci, Myriam
AU  - Decaussin-Petrucci M
AD  - 16 Service d'Anatomie et Cytologie Pathologiques, Groupement Hospitalier Lyon Sud 
      , Hospices Civils de Lyon, et Universite Lyon 1, France .
FAU - Schlumberger, Martin
AU  - Schlumberger M
AD  - 8 Service de Medecine Nucleaire et de Cancerologie Endocrinienne, Institut 
      Gustave Roussy , Villejuif et Universite Paris Saclay, France .
LA  - eng
SI  - ClinicalTrials.gov/NCT01830504
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Aminopyridines)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (NVP-BKM120)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
SB  - IM
MH  - Adenocarcinoma, Follicular/*drug therapy/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aminopyridines/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Disease Progression
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Morpholines/*therapeutic use
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Pilot Projects
MH  - Progression-Free Survival
MH  - Thyroid Cancer, Papillary/*drug therapy/pathology
MH  - Thyroid Neoplasms/*drug therapy/pathology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - PI3 kinase pathway
OT  - follicular thyroid carcinoma
OT  - poorly differentiated thyroid carcinoma
OT  - refractory thyroid cancer
OT  - targeted therapy
EDAT- 2018/08/15 06:00
MHDA- 2019/05/06 06:00
CRDT- 2018/08/15 06:00
PHST- 2018/08/15 06:00 [pubmed]
PHST- 2019/05/06 06:00 [medline]
PHST- 2018/08/15 06:00 [entrez]
AID - 10.1089/thy.2017.0663 [doi]
PST - ppublish
SO  - Thyroid. 2018 Sep;28(9):1174-1179. doi: 10.1089/thy.2017.0663.