title: Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072.
abstract: BACKGROUND
  Pazopanib recently received approval for the treatment of certain soft tissue sarcoma (STS) subtypes. We conducted a retrospective analysis on pooled data from two EORTC trials on pazopanib in STS in order to characterize long-term responders and survivors.
  
  
  METHODS
  Selected patients were treated with pazopanib in phase II (n = 118) and phase III study (PALETTE) (n = 226). Combined median progression-free survival (PFS) was 4.4 months; the median overall survival (OS) was 11.7 months. Thirty-six percent of patients had a PFS ≥ 6 months and were defined as long-term responders; 34% of patients survived ≥18 months, defined as long-term survivors. Patient characteristics were studied for their association with long-term outcomes.
  
  
  RESULTS
  The median follow-up was 2.3 years. Patient characteristics were compared among four subgroups based on short-/long-term PFS and OS, respectively. Seventy-six patients (22.1%) were both long-term responders and long-term survivors. The analysis confirmed the importance of known prognostic factors in metastatic STS patients treated with systemic treatment, such as performance status and tumor grading, and additionally hemoglobin at baseline as new prognostic factor. We identified 12 patients (3.5%) remaining on pazopanib for more than 2 years: nine aged younger than 50 years, nine females, four with smooth muscle tumors and nine with low or intermediate grade tumors at initial diagnosis. The median time on pazopanib in these patients was 2.4 years with the longest duration of 3.7 years.
  
  
  CONCLUSIONS
  Thirty-six percent and 34% of all STS patients who received pazopanib in these studies had a long PFS and/or OS, respectively. For more than 2 years, 3.5% of patients remained progression free under pazopanib. Good performance status, low/intermediate grade of the primary tumor and a normal hemoglobin level at baseline were advantageous for long-term outcome. NCT00297258 (phase II) and NCT00753688 (phase III, PALETTE).
authors: Interdisciplinary Tumor Center, Sarcoma Unit, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany. Electronic address: bernd.kasper@umm.de.
authors: B
authors: B
authors: Kasper
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: S
authors: S
authors: Sleijfer
authors: EORTC Data Centre, Brussels, Belgium.
authors: S
authors: S
authors: Litière
authors: EORTC Data Centre, Brussels, Belgium.
authors: S
authors: S
authors: Marreaud
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: J
authors: J
authors: Verweij
authors: Oncology TA Group, GlaxoSmithKline, Uxbridge, UK.
authors: R A
authors: RA
authors: Hodge
authors: Sarcoma Center, West German Cancer Center, Essen, Germany.
authors: S
authors: S
authors: Bauer
authors: Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam.
authors: J M
authors: JM
authors: Kerst
authors: Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: W T A
authors: WTA
authors: van der Graaf
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D010919:Placebos / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: EORTC; STBSG; long-term responders; long-term survivors; pazopanib; soft tissue sarcoma