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Clinical Studies

Phase II study of pazopanib with oral topotecan in patients with metastatic and non-resectable soft tissue and bone sarcomas



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.


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.


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.


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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Fig. 1: Progression-free survival for cohorts 1 (non-adipocytic soft-tissue sarcoma), 2 (osteosarcoma) and 3 (liposarcoma).
Fig. 2: Overall survival of cohort 1 (soft-tissue sarcoma), cohort 2 (osteosarcoma) and cohort 3 (liposarcoma).


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We are indebted to all the patients, and co-investigators who have participated in this trial. We want to thank the following collaborators of their assistance in preparation, and funding of this project.

Author information




Manuscript preparation: B.S., M.A. Study design: N.M., M.A. Patient data and study materials: M.M., S.A., S.R., V.M., A.H., P.O., J.C., S.A., R.C., S.O., B.V.T., M.A. Data analysis and interpretation: B.S., M.A., I.H. Manuscript editing and review: All.

Corresponding author

Correspondence to Mark Agulnik.

Ethics declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of each participating institution—Northwestern University, University of Iowa, Mayo Clinic, Medical College of Wisconsin and Washington University School of Medicine. Furthermore, written consent was obtained from all participants.

Consent to publish

Not applicable.

Data availability

All data are available upon request.

Competing interests

The authors declare no competing interests.

Funding information

Research was sponsored by Northwestern University, with limited collaborative support from Novartis Pharmaceuticals.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Schulte, B., Mohindra, N., Milhem, M. et al. Phase II study of pazopanib with oral topotecan in patients with metastatic and non-resectable soft tissue and bone sarcomas. Br J Cancer (2021).

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