PMID- 25962440
OWN - NLM
STAT- MEDLINE
DCOM- 20160405
LR  - 20220321
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 26
IP  - 7
DP  - 2015 Jul
TI  - Clinical usefulness of PI3K/Akt/mTOR genotyping in companion with other clinical 
      variables in metastatic renal cell carcinoma patients treated with everolimus in 
      the second and subsequent lines.
PG  - 1385-9
LID - 10.1093/annonc/mdv166 [doi]
AB  - BACKGROUND: The aim of this study was to search for predictive and prognostic 
      factors in patients with metastatic renal cell carcinoma (mRCC) treated with 
      everolimus among the components of PI3K/AKT/mTOR pathway. PATIENTS AND METHODS: 
      In a prospective, one-arm, phase II study, patients with mRCC received everolimus 
      (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential 
      biomarkers of PI3K/AKT/mTOR pathway. RESULTS: The median age of the 58 patients 
      enrolled into the study was 60 years (range 41-78 years). In multivariate 
      analysis, it was found that the adverse independent predictors for everolimus 
      therapy were histological grade G1/2 hazard ratio (HR): 2.68 [95% confidence 
      interval (CI) 1.29-5.58, P = 0.0082], increased lactate dehydrogenase (LDH) 
      level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA 
      gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 
      0.0254). In multivariate analysis, it was observed that the adverse independent 
      prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 
      1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA 
      versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)]. CONCLUSIONS: The PI3KCA gene 
      polymorphism, LDH, and histologic grade can predict the effects of everolimus 
      treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may 
      be independent prognostic factors. Further investigation is needed to confirm and 
      validate these findings prospectively in other RCC trials.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Bodnar, L
AU  - Bodnar L
AD  - Department of Oncology, Military Institute of Medicine, Warsaw, Poland 
      lubo@esculap.pl.
FAU - Stec, R
AU  - Stec R
AD  - Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
FAU - Cierniak, S
AU  - Cierniak S
AD  - Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
FAU - Synowiec, A
AU  - Synowiec A
AD  - Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
FAU - Wcislo, G
AU  - Wcislo G
AD  - Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
FAU - Jesiotr, M
AU  - Jesiotr M
AD  - Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
FAU - Koktysz, R
AU  - Koktysz R
AD  - Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
FAU - Kozlowski, W
AU  - Kozlowski W
AD  - Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
FAU - Szczylik, C
AU  - Szczylik C
AD  - Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150510
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Papillary/drug therapy/*genetics/mortality/secondary
MH  - Carcinoma, Renal Cell/drug therapy/*genetics/mortality/secondary
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - Everolimus/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - Humans
MH  - Kidney Neoplasms/drug therapy/*genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Neoplasm Grading
MH  - Phosphatidylinositol 3-Kinases/*genetics
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Prospective Studies
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics
OTO - NOTNLM
OT  - AKT
OT  - PI3KCA
OT  - everolimus
OT  - mTOR
OT  - renal cell carcinoma
EDAT- 2015/05/13 06:00
MHDA- 2016/04/06 06:00
CRDT- 2015/05/13 06:00
PHST- 2014/12/01 00:00 [received]
PHST- 2015/03/18 00:00 [accepted]
PHST- 2015/05/13 06:00 [entrez]
PHST- 2015/05/13 06:00 [pubmed]
PHST- 2016/04/06 06:00 [medline]
AID - S0923-7534(19)34492-8 [pii]
AID - 10.1093/annonc/mdv166 [doi]
PST - ppublish
SO  - Ann Oncol. 2015 Jul;26(7):1385-9. doi: 10.1093/annonc/mdv166. Epub 2015 May 10.