PMID- 33935721
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210504
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Improved Treatment Outcomes by Using Patient Specific Drug Combinations in 
      Mammalian Target of Rapamycin Activated Advanced Metastatic Cancers.
PG  - 631135
LID - 10.3389/fphar.2021.631135 [doi]
LID - 631135
AB  - Background: Activation of the mTOR signaling pathway is ubiquitous in cancers and 
      a favourable therapeutic target. However, presently approved mTOR inhibitor 
      monotherapies have modest benefits in labeled indications while poor outcomes 
      have been reported for mTOR inhibitor monotherapy when administered in a 
      label-agnostic setting based on univariate molecular indications. The present 
      study aimed to determine whether patient-specific combination regimens with mTOR 
      inhibitors and other anticancer agents selected based on multi-analyte molecular 
      and functional tumor interrogation (ETA: Encyclopedic Tumor Analysis) yields 
      significant treatment response and survival benefits in advanced or refractory 
      solid organ cancers. Methods: We evaluated treatment outcomes in 49 patients 
      diagnosed with unresectable or metastatic solid organ cancers, of whom 3 were 
      therapy naive and 46 were pre-treated in whom the cancer had progressed on 2 or 
      more prior systemic lines. All patients received mTOR inhibitor in combination 
      with other targeted, endocrine or cytotoxic agents as guided by ETA. Patients 
      were followed-up to determine Objective Response Rate (ORR), Progression Free 
      Survival (PFS) and Overall Survival (OS). Results: The Objective Response Rate 
      (ORR) was 57.1%, the disease Control rate (DCR) was 91.8%, median Progression 
      Free Survival (mPFS) was 4.9 months and median Overall Survival (mOS) was 9.4 
      months. There were no Grade IV treatment related adverse events (AEs) or any 
      treatment related deaths. Conclusion: Patient-specific combination regimens with 
      mTOR inhibition and other anti-neoplastic agents, when selected based on 
      multi-analyte molecular and functional profiling of the tumor can yield 
      meaningful outcomes in advanced or refractory solid organ cancers. Trial 
      Registration: Details of all trials are available at WHO-ICTRP: 
      https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011808. ACTPRO ID 
      CTRI/2018/05/014178. LIQUID IMPACT ID CTRI/2019/02/017548.
CI  - Copyright (c) 2021 Crook, Patil, Gaya, Plowman, Limaye, Ranade, Bhatt, Page and 
      Akolkar.
FAU - Crook, Timothy
AU  - Crook T
AD  - Broomfield Hospital, Chelmsford, United Kingdom.
FAU - Patil, Darshana
AU  - Patil D
AD  - Datar Cancer Genetics, Nasik, India.
FAU - Gaya, Andrew
AU  - Gaya A
AD  - HCA Healthcare United Kingdom, London, United Kingdom.
FAU - Plowman, Nicholas
AU  - Plowman N
AD  - St Bartholomew's Hospital, London, United Kingdom.
FAU - Limaye, Sewanti
AU  - Limaye S
AD  - Kokilaben Dhirubhai Ambani Hospital, Mumbai, India.
FAU - Ranade, Anantbhushan
AU  - Ranade A
AD  - Avinash Cancer Clinic, Pune, India.
FAU - Bhatt, Amit
AU  - Bhatt A
AD  - Avinash Cancer Clinic, Pune, India.
FAU - Page, Raymond
AU  - Page R
AD  - Worcester Polytechnic Institute, Worcester, India.
FAU - Akolkar, Dadasaheb
AU  - Akolkar D
AD  - Datar Cancer Genetics, Nasik, India.
LA  - eng
PT  - Journal Article
DEP - 20210416
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8085687
OTO - NOTNLM
OT  - Akt
OT  - ETA
OT  - PI3K
OT  - PIK3CA
OT  - encyclopedic tumor analysis
OT  - mTOR
OT  - mTOR inhibitor
OT  - rapalog
COIS- DP and DA are in full time employment of the Study Sponsor (DCG). All remaining 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest..
EDAT- 2021/05/04 06:00
MHDA- 2021/05/04 06:01
PMCR- 2021/04/16
CRDT- 2021/05/03 06:10
PHST- 2020/11/19 00:00 [received]
PHST- 2021/02/25 00:00 [accepted]
PHST- 2021/05/03 06:10 [entrez]
PHST- 2021/05/04 06:00 [pubmed]
PHST- 2021/05/04 06:01 [medline]
PHST- 2021/04/16 00:00 [pmc-release]
AID - 631135 [pii]
AID - 10.3389/fphar.2021.631135 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Apr 16;12:631135. doi: 10.3389/fphar.2021.631135. 
      eCollection 2021.