PMID- 25528496
OWN - NLM
STAT- MEDLINE
DCOM- 20150427
LR  - 20220408
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Linking)
VI  - 136
IP  - 2
DP  - 2015 Feb
TI  - Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients 
      with advanced or recurrent endometrial carcinoma.
PG  - 246-53
LID - S0090-8258(14)01574-1 [pii]
LID - 10.1016/j.ygyno.2014.12.019 [doi]
AB  - OBJECTIVE: Patients with endometrial carcinoma who progress after first-line 
      chemotherapy have a poor prognosis. Phosphoinositide 3-kinase (PI3K) inhibitors 
      are investigational treatment options in this setting. This study evaluated the 
      efficacy and safety of the PI3K inhibitor pilaralisib (SAR245408; XL147) in 
      advanced or recurrent endometrial carcinoma. METHODS: This Phase II, multicenter, 
      single-arm, open-label study enrolled patients with histologically confirmed 
      advanced or recurrent endometrial carcinoma, who had received one or two prior 
      chemotherapy regimens. Patients received pilaralisib 600mg capsules or 400mg 
      tablets once daily. Primary endpoints were objective response rate (ORR), 
      proportion of patients with progression-free survival (PFS) >6months and safety. 
      Molecular profiling in archival tumor tissue and circulating tumor DNA were 
      performed to identify molecular markers associated with response or resistance to 
      pilaralisib. RESULTS: 67 patients were enrolled, of which 50 and 17 patients had 
      received one or two prior regimens, respectively. Complete or partial tumor 
      responses occurred in two patients each (ORR 6.0%); three had tumors with normal 
      PTEN expression and PIK3R1 mutations and one had a tumor with PTEN protein 
      deficiency. However, there was no association between molecular alterations and 
      clinical activity. Rate of PFS>6months was 11.9%. The most commonly reported 
      treatment-related adverse events (AEs) were rash (40.3%), diarrhea (37.3%) and 
      fatigue (28.4%). The most commonly reported treatment-related grade >/=3 AEs were 
      rash (9.0%), diarrhea (4.5%) and increased alanine aminotransferase (4.5%). 
      CONCLUSIONS: Pilaralisib was associated with a favorable safety profile and 
      minimal antitumor activity in advanced or recurrent endometrial carcinoma.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Matulonis, Ursula
AU  - Matulonis U
AD  - Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: 
      Ursula_Matulonis@dfci.harvard.edu.
FAU - Vergote, Ignace
AU  - Vergote I
AD  - Leuven Cancer Institute, Leuven, European Union, Belgium.
FAU - Backes, Floor
AU  - Backes F
AD  - Ohio State University, Columbus, OH, USA.
FAU - Martin, Lainie P
AU  - Martin LP
AD  - Fox Chase Cancer Center, Philadelphia, PA, USA.
FAU - McMeekin, Scott
AU  - McMeekin S
AD  - University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
FAU - Birrer, Michael
AU  - Birrer M
AD  - Massachusetts General Hospital Cancer Center, Boston, MA, USA.
FAU - Campana, Frank
AU  - Campana F
AD  - Sanofi, Cambridge, MA, USA.
FAU - Xu, Yi
AU  - Xu Y
AD  - Sanofi, Cambridge, MA, USA.
FAU - Egile, Coumaran
AU  - Egile C
AD  - Sanofi Oncology, Vitry sur Seine, France.
FAU - Ghamande, Sharad
AU  - Ghamande S
AD  - Georgia Regents University Cancer Center, Augusta, GA, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141217
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 0 (XL147)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/administration & dosage/adverse effects
MH  - Endometrial Neoplasms/*drug therapy/enzymology
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/enzymology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects
MH  - Quinoxalines/*administration & dosage/adverse effects
MH  - Sulfonamides/*administration & dosage/adverse effects
OTO - NOTNLM
OT  - Endometrial cancer
OT  - PI3K inhibitors
EDAT- 2014/12/22 06:00
MHDA- 2015/04/29 06:00
CRDT- 2014/12/22 06:00
PHST- 2014/10/15 00:00 [received]
PHST- 2014/12/02 00:00 [revised]
PHST- 2014/12/09 00:00 [accepted]
PHST- 2014/12/22 06:00 [entrez]
PHST- 2014/12/22 06:00 [pubmed]
PHST- 2015/04/29 06:00 [medline]
AID - S0090-8258(14)01574-1 [pii]
AID - 10.1016/j.ygyno.2014.12.019 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2015 Feb;136(2):246-53. doi: 10.1016/j.ygyno.2014.12.019. Epub 
      2014 Dec 17.