title: Response to anti-PD1 therapy with nivolumab in metastatic sarcomas.
abstract: BACKGROUND
  Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express PD-1 ligand.
  
  
  METHODS
  We retrospectively analyzed a cohort of patients (pts) with relapsed metastatic/unresectable sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least four doses of nivolumab; RECIST 1.1 criteria were used for response assessment.
  
  
  RESULTS
  Twenty-eight pts with soft tissue (STS, N = 24) or bone sarcoma (N = 4), received IV nivolumab 3 mg/kg every 2 weeks from July 2015. Median age was 57 (24-78), male:female ratio was 14:14; the median number of nivolumab cycles was eight. Eighteen pts concomitantly received pazopanib at 400-800 mg daily. The most common side effect was grade 1-2 LFT elevations; grade 3-4 toxicity occurred in five patients (colitis, LFT elevations, pneumonitis). Twenty-four pts received at least four cycles. We observed three partial responses: one dedifferentiated chondrosarcoma, one epithelioid sarcoma and one maxillary osteosarcoma (last two patients on pazopanib); nine patients had stable disease including three leiomyosarcomas; 12 patients had progression of disease including 4 leiomyosarcoma. Clinical benefit (response + stability) was observed in 50% of the evaluable patients.
  
  
  CONCLUSIONS
  These data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and bone sarcoma.
authors.affiliation: Department of Medicine, NYU Langone Medical Center, New York, NY USA.
authors.forename: L
authors.identifier: 0000-0002-2656-5224
authors.initials: L
authors.lastname: Paoluzzi
authors.affiliation: Department of Medicine, NYU Langone Medical Center, New York, NY USA.
authors.forename: A
authors.initials: A
authors.lastname: Cacavio
authors.affiliation: Department of Radiology, NYU Langone Medical Center, New York, NY USA.
authors.forename: M
authors.initials: M
authors.lastname: Ghesani
authors.affiliation: Department of Radiology, NYU Langone Medical Center, New York, NY USA.
authors.forename: A
authors.initials: A
authors.lastname: Karambelkar
authors.affiliation: Department of Pathology, New York University School of Medicine, Laura and Isaac Perlmutter Cancer Center, 10th floor, Room 1041, 160 East 34th street, New York, NY USA.
authors.forename: A
authors.initials: A
authors.lastname: Rapkiewicz
authors.affiliation: Department of Medicine, NYU Langone Medical Center, New York, NY USA.
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.affiliation: Department of Medicine, NYU Langone Medical Center, New York, NY USA.
authors.forename: G
authors.initials: G
authors.lastname: Rosen
keywords: Check point inhibitors; Immunotherapy; Nivolumab; PD-1; Sarcoma