Brian Schulte1, Nisha Mohindra1, Mohammed Milhem2, Steven Attia3, Steven Robinson4, Varun Monga2, Angela C Hirbe5, Peter Oppelt5, John Charlson6, Irene Helenowski7, Susan Abbinanti1, Rasima Cehic1, Scott Okuno4, Brian A Van Tine5, Mark Agulnik8,9. 1. Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 2. Department of Internal Medicine, Division of Hematology/Oncology and BMT, University of Iowa, Iowa City, IA, USA. 3. Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA. 4. Department of Oncology, Mayo Clinic, Rochester, MN, USA. 5. Division of Medical Oncology at Washington University School of Medicine/Siteman Cancer Center, St Louis, MO, USA. 6. Department of Medical Oncology, Medical College of Wisconsin, Wauwatosa, WI, USA. 7. Department of Preventative Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 8. Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. magulnik@coh.org. 9. Department of Medical Oncology, City of Hope, Duarte, CA, USA. magulnik@coh.org.
Abstract
BACKGROUND: Pazopanib is active in refractory soft-tissue sarcoma (STS) and significantly prolongs PFS. Prior studies of combinations of metronomic topotecan with pazopanib have indicated preclinical evidence of response in patients with sarcoma. METHODS: This prospective, single arm, phase II study evaluated the efficacy of the combination of pazopanib with topotecan in patients with metastatic or unresectable non-adipocytic STS. Furthermore, it incorporated exploratory arms for osteosarcoma and liposarcoma. The primary endpoint was progression-free rate at 12 weeks in the non-adipocytic STS cohort. RESULTS: 57.5% of patients in the non-adipocytic STS cohort were progression free at 12 weeks, which did not meet the primary endpoint of the study (66%). The exploratory osteosarcoma cohort exceeded previously established phase II trial comparator data benchmark of 12% with a PFR at 12 weeks of 69.55%. Treatment with the combination of pazopanib and topotecan was accompanied by a grade 3 or 4 toxicities in most patients. CONCLUSIONS: In this prospective trial in refractory metastatic or unresectable STS and osteosarcoma, the combination of pazopanib with topotecan did not meet its primary endpoint of progression-free rate at 12 weeks. The combination of pazopanib with topotecan was associated with a high degree of toxicity.
BACKGROUND: Pazopanib is active in refractory soft-tissue sarcoma (STS) and significantly prolongs PFS. Prior studies of combinations of metronomic topotecan with pazopanib have indicated preclinical evidence of response in patients with sarcoma. METHODS: This prospective, single arm, phase II study evaluated the efficacy of the combination of pazopanib with topotecan in patients with metastatic or unresectable non-adipocytic STS. Furthermore, it incorporated exploratory arms for osteosarcoma and liposarcoma. The primary endpoint was progression-free rate at 12 weeks in the non-adipocytic STS cohort. RESULTS: 57.5% of patients in the non-adipocytic STS cohort were progression free at 12 weeks, which did not meet the primary endpoint of the study (66%). The exploratory osteosarcoma cohort exceeded previously established phase II trial comparator data benchmark of 12% with a PFR at 12 weeks of 69.55%. Treatment with the combination of pazopanib and topotecan was accompanied by a grade 3 or 4 toxicities in most patients. CONCLUSIONS: In this prospective trial in refractory metastatic or unresectable STS and osteosarcoma, the combination of pazopanib with topotecan did not meet its primary endpoint of progression-free rate at 12 weeks. The combination of pazopanib with topotecan was associated with a high degree of toxicity.
Authors: Joanne P Lagmay; Mark D Krailo; Ha Dang; AeRang Kim; Douglas S Hawkins; Orren Beaty; Brigitte C Widemann; Theodore Zwerdling; Lisa Bomgaars; Anne-Marie Langevin; Holcombe E Grier; Brenda Weigel; Susan M Blaney; Richard Gorlick; Katherine A Janeway Journal: J Clin Oncol Date: 2016-07-11 Impact factor: 44.544
Authors: Patrick Schöffski; Sant Chawla; Robert G Maki; Antoine Italiano; Hans Gelderblom; Edwin Choy; Giovanni Grignani; Veridiana Camargo; Sebastian Bauer; Sun Young Rha; Jean-Yves Blay; Peter Hohenberger; David D'Adamo; Matthew Guo; Bartosz Chmielowski; Axel Le Cesne; George D Demetri; Shreyaskumar R Patel Journal: Lancet Date: 2016-02-10 Impact factor: 79.321
Authors: Jaap Verweij; Paolo G Casali; John Zalcberg; Axel LeCesne; Peter Reichardt; Jean-Yves Blay; Rolf Issels; Allan van Oosterom; Pancras C W Hogendoorn; Martine Van Glabbeke; Rossella Bertulli; Ian Judson Journal: Lancet Date: 2004 Sep 25-Oct 1 Impact factor: 79.321
Authors: Peter Reichardt; Karin Oechsle; Daniel Pink; Carsten Bokemeyer; F Schneller; Rolf Issels; Lothar Kanz; Jörg Thomas Hartmann Journal: Invest New Drugs Date: 2003-11 Impact factor: 3.850
Authors: B Milojkovic Kerklaan; M P J Lolkema; L A Devriese; E E Voest; A Nol-Boekel; M Mergui-Roelvink; M Langenberg; K Mykulowycz; J Stoebenau; S Lane; P Legenne; P Wissel; D A Smith; B J Giantonio; J H M Schellens; P O Witteveen Journal: Br J Cancer Date: 2015-08-20 Impact factor: 7.640
Authors: Arif Manji; Yvan Samson; Rebecca J Deyell; Donna L Johnston; Victor A Lewis; Alexandra P Zorzi; Jason N Berman; Kathy Brodeur-Robb; Ellen Morrison; Lynn Kee; Sushil Kumar; Sylvain Baruchel; James A Whitlock; Daniel A Morgenstern Journal: Cancers (Basel) Date: 2022-06-17 Impact factor: 6.575