Viktor Grünwald1,2, Annika Karch3, Markus Schuler4, Patrick Schöffski5, Hans-Georg Kopp6, Sebastian Bauer7, Bernd Kasper8, Lars H Lindner9, Jens-Marcus Chemnitz10,11, Martina Crysandt12, Alexander Stein13, Björn Steffen14, Stephan Richter15, Gerlinde Egerer16, Philipp Ivanyi1, Silke Zimmermann17, Xiaofei Liu3, Annegret Kunitz18,19. 1. Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Medical School Hannover, Hannover, Germany. 2. Interdisciplinary Genitourinary Oncology at the West-German Cancer Center, Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University Hospital Essen, Essen, Germany. 3. Institute for Biostatistics, Medical School Hannover, Hannover, Germany. 4. Helios Clinic, Berlin, Germany. 5. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Katholieke Universiteit Leuven, Leuven, Belgium. 6. Robert Bosch Centrum für Tumorerkrankungen Stuttgart, Stuttgart, Germany. 7. Clinic for Internal Medicine (Tumor Research), University Hospital Essen, Essen, Germany. 8. Sarcoma Unit, Mannheim University Medical Center, Mannheim, Germany. 9. Department of Medicine III, University Hospital, Ludwig Maximilian University Munich, Munich, Germany. 10. Community Hospital Middle Rine, Middle Rine, Germany. 11. Department of Hematology, Oncology, Clinical Infectious Diseases, Clinical Immunology, Hemostaseology and Medical Intensive Care, University Hospital Cologne, Cologne, Germany. 12. University Hospital Aachen, Aachen, Germany. 13. University Hospital Hamburg-Eppendorf, Hamburg-Eppendorf, Germany. 14. University Hospital Frankfurt, Frankfurt, Germany. 15. University Hospital Carl Gustav Carus, University Cancer Center/Medical Department I, Dresden, Germany. 16. University Hospital Heidelberg, Heidelberg, Germany. 17. Hannover Clinical Trial Center, Hannover, Germany. 18. Vivantes Clinic Berlin-Spandau, Berlin-Spandau, Germany. 19. Department of Hematology, Oncology and Tumor Immunology, University Hospital Charite, Berlin, Germany.
Abstract
PURPOSE:Doxorubicin is a standard of care in patients with advanced, inoperable soft tissue sarcoma (STS). We tested whether pazopanib has efficacy comparable to that of doxorubicin in elderly patients with STS and offers superior tolerability for hematologic toxicity. PATIENTS AND METHODS: Patients age 60 years or older without previous systemic treatment for progressive advanced or metastatic STS who had Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were included. Treatment consisted of pazopanib 800 mg once per day or doxorubicin 75 mg/m2 once every 3 weeks (≤ 6 cycles) after being randomly assigned in a 2:1 ratio. Noninferiority was assumed for progression-free survival (PFS), if the upper limit of the 95% CI for the hazard ratio (HR) was less than 1.8. Neutropenia and febrile neutropenia were key secondary end points. The European Organisation for Research and Treatment of Cancer (30-item) Quality of Life Questionnaire and geriatric assessment were used to measure patient-reported outcomes. Cox regression analysis and Kaplan-Meier curves were used for analysis. RESULTS:Pazopanib and doxorubicin were given to 81 and 39 patients, respectively. The median age was 71 years (range, 60-88 years). PFS was noninferior (HR, 1.00; 95% CI, 0.65 to 1.53) and the incidence of grade 4 neutropenia and febrile neutropenia favored pazopanib. Objective response rates for pazopanib and doxorubicin were 12.3% and 15.4%, respectively. Overall survival did not differ significantly between arms (HR, 1.08; 95% CI, 0.68 to 1.72; P = .735). Geriatric assessment revealed 2 or more comorbidities in 15.8% of the patients and impairment of activities of daily living in 28.3% of patients. CONCLUSION:Pazopanib was noninferior to doxorubicin, rendering pazopanib a putative therapeutic option in the first-line treatment of STS in patients age 60 years or older. The distinct adverse event profile may be used to counsel patients and tailor therapy to individual needs.
RCT Entities:
PURPOSE:Doxorubicin is a standard of care in patients with advanced, inoperable soft tissue sarcoma (STS). We tested whether pazopanib has efficacy comparable to that of doxorubicin in elderly patients with STS and offers superior tolerability for hematologic toxicity. PATIENTS AND METHODS: Patients age 60 years or older without previous systemic treatment for progressive advanced or metastatic STS who had Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were included. Treatment consisted of pazopanib 800 mg once per day or doxorubicin 75 mg/m2 once every 3 weeks (≤ 6 cycles) after being randomly assigned in a 2:1 ratio. Noninferiority was assumed for progression-free survival (PFS), if the upper limit of the 95% CI for the hazard ratio (HR) was less than 1.8. Neutropenia and febrile neutropenia were key secondary end points. The European Organisation for Research and Treatment of Cancer (30-item) Quality of Life Questionnaire and geriatric assessment were used to measure patient-reported outcomes. Cox regression analysis and Kaplan-Meier curves were used for analysis. RESULTS:Pazopanib and doxorubicin were given to 81 and 39 patients, respectively. The median age was 71 years (range, 60-88 years). PFS was noninferior (HR, 1.00; 95% CI, 0.65 to 1.53) and the incidence of grade 4 neutropenia and febrile neutropenia favored pazopanib. Objective response rates for pazopanib and doxorubicin were 12.3% and 15.4%, respectively. Overall survival did not differ significantly between arms (HR, 1.08; 95% CI, 0.68 to 1.72; P = .735). Geriatric assessment revealed 2 or more comorbidities in 15.8% of the patients and impairment of activities of daily living in 28.3% of patients. CONCLUSION:Pazopanib was noninferior to doxorubicin, rendering pazopanib a putative therapeutic option in the first-line treatment of STS in patients age 60 years or older. The distinct adverse event profile may be used to counsel patients and tailor therapy to individual needs.
Authors: Brian Schulte; Nisha Mohindra; Mohammed Milhem; Steven Attia; Steven Robinson; Varun Monga; Angela C Hirbe; Peter Oppelt; John Charlson; Irene Helenowski; Susan Abbinanti; Rasima Cehic; Scott Okuno; Brian A Van Tine; Mark Agulnik Journal: Br J Cancer Date: 2021-05-28 Impact factor: 9.075
Authors: Marie A Flannery; Eva Culakova; Beverly E Canin; Luke Peppone; Erika Ramsdale; Supriya G Mohile Journal: J Clin Oncol Date: 2021-05-27 Impact factor: 44.544
Authors: Natalia I Moiseeva; Lidia A Laletina; Timur I Fetisov; Leyla F Makhmudova; Angelika E Manikaylo; Liliya Y Fomina; Denis A Burov; Ekaterina A Lesovaya; Beniamin Y Bokhyan; Victoria Y Zinovieva; Alice S Vilkova; Larisa V Mekheda; Nikolay A Kozlov; Alexander M Scherbakov; Evgeny M Kirilin; Gennady A Belitsky; Marianna G Yakubovskaya; Kirill I Kirsanov Journal: Int J Mol Sci Date: 2022-03-16 Impact factor: 5.923