Phase II study of pazopanib with oral topotecan in patients with metastatic and non-resectable soft tissue and bone sarcomas
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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.
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Although multi-targeted tyrosine kinase inhibitors can induce measurable responses, durable disease control continues to be a major challenge.
“Although multi-targeted TKIs can induce measurable responses, durable disease control continues to be a major challenge1,4–6,13,14,18.”
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- Authors
- Schulte, B., Mohindra, N., Milhem, M., Attia, S., Robinson, S., Monga, V., Hirbe, A. C., Oppelt, P., Charlson, J., Helenowski, I., Abbinanti, S., Cehic, R., Okuno, S., Van Tine, B. A., & Agulnik, M.
- Affiliations
- Northwestern University (US)
- University of Iowa (US)
- Mayo Clinic in Florida (US)
- Mayo Clinic (US)
- Washington University in St. Louis (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Agulnik, Mark
- ORCID
- Venue
- British Journal of Cancer
- Published
- 2021-05-28
- Volume
- 125
- Issue
- 4
- Pages
- 528-533
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC8368095
- OpenAlex
- W3164260637
- Cited by
- 19
- References
- 27
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 2 · 2018: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Cancer (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Novartis Pharmaceuticals Corporation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Health Sciences › Medicine › Oncology › Vascular Tumors and Angiosarcomas
- Keywords
- pazopanib, topotecan, soft tissue sarcoma, osteosarcoma, liposarcoma, metastatic sarcoma, combination chemotherapy, progression-free rate, drug toxicity
- MeSH terms
- Administration, Oral, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Drug Administration Schedule, Humans, Indazoles, Male, Middle Aged, Neoplasm Metastasis, Prospective Studies, Pyrimidines, Sarcoma, Osteosarcoma, Sulfonamides, Treatment Outcome, Disease-Free Survival, Topotecan, Young Adult
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