title: Imatinib induces sustained progression arrest in RECIST progressive desmoid tumours: Final results of a phase II study of the German Interdisciplinary Sarcoma Group (GISG).
abstract: Desmoid tumours describe a rare monoclonal, fibroblastic proliferation characterised by an often unpredictable clinical course. Surgery is one therapeutic option for progressing patients, except if mutilating and associated with considerable function loss. Different systemic treatment approaches have been investigated and promising results could be demonstrated using imatinib.
  
  
  
  We initiated a phase II trial within the German Interdisciplinary Sarcoma Group (GISG) evaluating imatinib to induce progression arrest in desmoid tumour patients being Response Evaluation Criteria in Solid Tumours (RECIST) progressive, not amenable to surgical resection with R0 intent or accompanied by unacceptable function loss (NCT01137916). Thirty-eight patients (median age 44 years [range: 19-80]; 68% female; 90% Eastern Cooperative Oncology Group (ECOG) performance status 0) were treated with a daily dose of 800 mg imatinib planned over 2 years. The progression arrest rate after 6 months of imatinib treatment (PAR6mo) was the primary end-point. Patients showing disease progression under imatinib could be treated with nilotinib 800 mg daily. Accrual started in July 2010 in four GISG centres and finalised in September 2013.
  
  
  
  The final analysis for the primary end-point in the evaluable patients of the full analysis set revealed a PAR6moof 65%. Subsequent progression arrest rates at 9, 12, 15, 18, 21 and 24 months were 65%, 59%, 53%, 53%, 50% and 45%, respectively. None of the patients died within the study observational period. Best reported response was seven partial responses at 21 months revealing an overall response rate of 19%. Eight patients treated with nilotinib demonstrated a PAR at 3 months of 88% (7/8); no more disease progressions occurred until end of study. In general imatinib adverse events were mild to moderate.
  
  
  
  Imatinib induces sustained progression arrest in RECIST progressive desmoid tumour patients. In addition, nilotinib had the potential to stabilise desmoid tumour growth after treatment failure with imatinib.
authors.affiliation: University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. Electronic address: bernd.kasper@umm.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kasper
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Gruenwald
authors.affiliation: HELIOS Klinikum Berlin-Buch, Sarcoma Center Berlin-Brandenburg, Schwanebecker Chaussee 50, D-13125 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Reichardt
authors.affiliation: Sarcoma Center, West German Cancer Center, Hufelandstr. 55, D-45122 Essen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.affiliation: University of Heidelberg, Institute of Medical Biometry and Informatics, Im Neuenheimer Feld 130.3, D-69120 Heidelberg, Germany.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Rauch
authors.affiliation: University of Heidelberg, Institute of Medical Biometry and Informatics, Im Neuenheimer Feld 130.3, D-69120 Heidelberg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Limprecht
authors.affiliation: University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Sommer
authors.affiliation: Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Dimitrakopoulou-Strauss
authors.affiliation: University of Heidelberg, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Pilz
authors.affiliation: Institute of Pathology, Friedrich Alexander University, Erlangen-Nürnberg, Krankenhausstr. 8-10, D-91054 Erlangen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Haller
authors.affiliation: University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany; University of Heidelberg, Mannheim University Medical Center, Division of Surgical Oncology, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
mesh_terms: D000008:Abdominal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D034861:Abdominal Wall / Q000000981:diagnostic imaging; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005121:Extremities / Q000000981:diagnostic imaging; D005260:Female; D018222:Desmoid Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000000981:diagnostic imaging / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000627:therapeutic use*; D066066:Response Evaluation Criteria in Solid Tumors; D012186:Retroperitoneal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D012983:Soft Tissue Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D013899:Thoracic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D035441:Thoracic Wall / Q000000981:diagnostic imaging; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib
keywords: Desmoid tumour; Imatinib; Nilotinib; Positron emission tomography; Progression arrest