title: SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma.
abstract: BACKGROUND
  Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma.
  
  
  METHODS
  Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%.
  
  
  RESULTS
  A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients.
  
  
  CONCLUSIONS
  Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Schuetze
authors.affiliation: Department of Biostatistics, Johnson & Johnson, New Brunswick, New Jersey.
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Wathen
authors.affiliation: Anatomic Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: David R
authors.initials: DR
authors.lastname: Lucas
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Northwest Oncology, Post Falls, Idaho.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Samuels
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Staddon
authors.affiliation: Medical Oncology, Stanford Medical Institute, Stanford, California.
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Ganjoo
authors.affiliation: Division of Medical Oncology and Hematology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope Medical Center, Duarte, California.
authors.forename: Warren A
authors.initials: WA
authors.lastname: Chow
authors.affiliation: Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: David M
authors.initials: DM
authors.lastname: Loeb
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Hussein A
authors.initials: HA
authors.lastname: Tawbi
authors.affiliation: Divison of Hematology/Oncology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Rushing
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Shreyaskumar R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: Molecular Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chugh
authors.affiliation: Sarcoma Alliance for Research through Collaboration, Ann Arbor, Michigan.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Reinke
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001499:Bayes Theorem; D000069439:Dasatinib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069439:Dasatinib
keywords: Bayesian; Choi; adaptive; dasatinib; phase 2; sarcoma