PMID- 29408858
OWN - NLM
STAT- MEDLINE
DCOM- 20180402
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 2
DP  - 2018
TI  - Efficacy of PI3K/AKT/mTOR pathway inhibitors for the treatment of advanced solid 
      cancers: A literature-based meta-analysis of 46 randomised control trials.
PG  - e0192464
LID - 10.1371/journal.pone.0192464 [doi]
LID - e0192464
AB  - BACKGROUND: The phosphatidylinositol-3- kinase (PI3K)/AKT/mammalian target of 
      rapamycin (mTOR) pathway (PI3K/AKT/mTOR pathway) plays a key role in cancer. We 
      performed this meta-analysis to assess the clinical effect of using PI3K/AKT/mTOR 
      pathway inhibitors on advanced solid tumours. METHODS: All the randomised 
      controlled trials (RCT) that compared the therapy with PI3K/AKT/mTOR pathway 
      inhibitors with other therapies were included. The main end-point was 
      progression-free survival (PFS); other end-points included overall survival (OS) 
      and objective response rate (ORR). A subgroup analysis was performed mainly for 
      PFS. RESULTS: In total, 46 eligible RCT were included. The pooled results showed 
      that PI3K/AKT/mTOR pathway inhibitor-based regimens significantly improved the 
      PFS of patients with advanced solid tumours (hazard ratios (HR) = 0.79; 95% 
      confidence intervals (CI): 0.71-0.88) and PI3K pathway mutations (HR = 0.69; 95% 
      CI: 0.56-0.85). All single PI3K/AKT/mTOR pathway inhibitor therapies were 
      compared with other targeted therapies (HR = 0.99; 95% CI: 0.93-1.06) and dual 
      targeted therapies, including PI3K/AKT/mTOR pathway inhibitors and other targeted 
      therapies (HR = 1.04; 95% CI: 0.62-1.74), which showed no significant differences 
      in the PFS. Additional PI3K/AKT/mTOR pathway inhibitors showed no advantage with 
      respect to the OS (HR = 0.98; 95% CI: 0.90-1.07) or ORR (risk ratio (RR) = 1.02; 
      95% CI: 0.87-1.20). CONCLUSION: Our meta-analysis results suggest that the 
      addition of the PI3K pathway inhibitors to the therapy regiment for advanced 
      solid tumours significantly improves PFS. The way that patients are selected to 
      receive the PI3K pathway inhibitors might be more meaningful in the future.
FAU - Li, Xuan
AU  - Li X
AUID- ORCID: 0000-0003-2851-8963
AD  - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, China.
FAU - Dai, Danian
AU  - Dai D
AD  - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, China.
FAU - Chen, Bo
AU  - Chen B
AD  - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, China.
FAU - Tang, Hailin
AU  - Tang H
AD  - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, China.
FAU - Xie, Xiaoming
AU  - Xie X
AD  - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, China.
FAU - Wei, Weidong
AU  - Wei W
AD  - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20180206
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Neoplasms/*drug therapy
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism
MH  - *Randomized Controlled Trials as Topic
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
PMC - PMC5800666
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/02/07 06:00
MHDA- 2018/04/03 06:00
PMCR- 2018/02/06
CRDT- 2018/02/07 06:00
PHST- 2017/10/27 00:00 [received]
PHST- 2018/01/23 00:00 [accepted]
PHST- 2018/02/07 06:00 [entrez]
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2018/04/03 06:00 [medline]
PHST- 2018/02/06 00:00 [pmc-release]
AID - PONE-D-17-37527 [pii]
AID - 10.1371/journal.pone.0192464 [doi]
PST - epublish
SO  - PLoS One. 2018 Feb 6;13(2):e0192464. doi: 10.1371/journal.pone.0192464. 
      eCollection 2018.