title: Outcome of uterine sarcoma patients treated with pazopanib: A retrospective analysis based on two European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) clinical trials 62043 and 62072.
abstract: BACKGROUND
  Uterine sarcomas are a group of mesenchymal tumours comprising several histologies. They have a high recurrence rate following surgery, modest outcome to systemic therapy, and poor overall survival. Pazopanib is a multi-targeted tyrosine kinase inhibitor approved for non-adipocytic advanced soft tissue sarcomas (STS). Here we investigated whether response to pazopanib in patients with uterine sarcomas differs from that of patients with non-uterine sarcomas.
  
  
  METHODS
  Uterine sarcoma patients were retrieved from all soft tissue sarcoma patients treated with pazopanib in EORTC Phase II (n=10) and Phase III (PALETTE) (n=34) studies. Patient and tumour characteristics, response, progression free and overall survival data were compared.
  
  
  RESULTS
  Forty-four patients with uterine sarcoma were treated with pazopanib. The majority of patients had uterine leiomyosarcoma (LMS) (n=39, 88.6%) with high grade tumours (n=37, 84.1%) compared to 54.8% (n=164) in the non-uterine population. The median age was 55years (range 33-79) and median follow up was 2.3years. Uterine patients were heavily pre-treated, 61.3% having ≥2 lines of chemotherapy prior to pazopanib compared to 40.8% in the non-uterine population. Five patients (11%), all LMS, had a partial response (95% CI 3.8-24.6). Median progression free survival (PFS) 3.0months (95% CI 2.5-4.7) in uterine versus 4.5 (95% CI 3.7-5.1) in non-uterine STS. Median overall survival (OS) was 17.5months (95% CI 11.1-19.6), longer than the non-uterine population, 11.1months (95% CI 10.2-12.0) (p=0.352).
  
  
  CONCLUSIONS
  Despite heavy pre-treatment, pazopanib shows signs of activity in patients with uterine sarcoma with the similar outcomes to patients with non-uterine STS.
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK. Electronic address: charlotte.benson@rmh.nhs.uk.
authors.forename: C
authors.initials: C
authors.lastname: Benson
authors.affiliation: Centre Leon Berard, University Claude Bernard, Lyon, France.
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sleijfer
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Litière
authors.affiliation: Centre Leon Berard, University Claude Bernard, Lyon, France.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
authors.affiliation: Military Hospital-State Health Centre, Budapest, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Papai
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Judson
authors.affiliation: University Hospitals Leuven-KU Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.affiliation: Sarcoma Oncology Centre, Santa Monica, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chawla
authors.affiliation: Institut Jules Bordet, Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Gil
authors.affiliation: Institut Curie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Marréaud
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: M R
authors.initials: MR
authors.lastname: Dewji
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK.
authors.forename: W T A
authors.initials: WTA
authors.lastname: van der Graaf
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007191:Indazoles; D007890:Leiomyosarcoma / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: Pazopanib; Soft tissue sarcoma; Uterine sarcoma