Bernd Kasper1, Viktor Gruenwald2, Peter Reichardt3, Sebastian Bauer4, Geraldine Rauch5, Ronald Limprecht5, Michaela Sommer6, Antonia Dimitrakopoulou-Strauss7, Lothar Pilz8, Florian Haller9, Peter Hohenberger10. 1. 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. 2. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. 3. HELIOS Klinikum Berlin-Buch, Sarcoma Center Berlin-Brandenburg, Schwanebecker Chaussee 50, D-13125 Berlin, Germany. 4. Sarcoma Center, West German Cancer Center, Hufelandstr. 55, D-45122 Essen, Germany. 5. University of Heidelberg, Institute of Medical Biometry and Informatics, Im Neuenheimer Feld 130.3, D-69120 Heidelberg, Germany. 6. University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. 7. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. 8. University of Heidelberg, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. 9. Institute of Pathology, Friedrich Alexander University, Erlangen-Nürnberg, Krankenhausstr. 8-10, D-91054 Erlangen, Germany. 10. 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.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: The final analysis for the primary end-point in the evaluable patients of the full analysis set revealed a PAR6mo of 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. CONCLUSIONS: 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.
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: The final analysis for the primary end-point in the evaluable patients of the full analysis set revealed a PAR6mo of 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. CONCLUSIONS: 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: Joanna Robles; Vahakn S Keskinyan; Matthew Thompson; Joseph T Davis; David Van Mater Journal: Pediatr Hematol Oncol Date: 2020-03-04 Impact factor: 1.969
Authors: Danielle Braggio; David Koller; Feng Jin; Nanda Siva; Abeba Zewdu; Gonzalo Lopez; Kara Batte; Lucia Casadei; Meng Welliver; Anne M Strohecker; Dina Lev; Raphael E Pollock Journal: Cancer Date: 2019-04-12 Impact factor: 6.860