title: Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma.
abstract: 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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: Ursula_Matulonis@dfci.harvard.edu.
authors.forename: Ursula
authors.initials: U
authors.lastname: Matulonis
authors.affiliation: Leuven Cancer Institute, Leuven, European Union, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Ohio State University, Columbus, OH, USA.
authors.forename: Floor
authors.initials: F
authors.lastname: Backes
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Lainie P
authors.initials: LP
authors.lastname: Martin
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: McMeekin
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Birrer
authors.affiliation: Sanofi, Cambridge, MA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Campana
authors.affiliation: Sanofi, Cambridge, MA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Sanofi Oncology, Vitry sur Seine, France.
authors.forename: Coumaran
authors.initials: C
authors.lastname: Egile
authors.affiliation: Georgia Regents University Cancer Center, Augusta, GA, USA.
authors.forename: Sharad
authors.initials: S
authors.lastname: Ghamande
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000201:enzymology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011810:Quinoxalines / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D013449:Sulfonamides; C581157:XL147
keywords: Endometrial cancer; PI3K inhibitors