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Poster Discussion session - Sarcoma

4770 - A Phase II Study of pazopanib with Oral Topotecan in Patients with Metastatic Osteosarcoma


22 Oct 2018


Poster Discussion session - Sarcoma


Cytotoxic Therapy

Tumour Site

Bone Sarcomas


Brian Van Tine


Annals of Oncology (2018) 29 (suppl_8): viii576-viii595. 10.1093/annonc/mdy299


B.A. Van Tine1, N. Mohindra2, M. Milhem3, S. Attia4, S.I. Robinson5, A. Rademaker6, S.H. Okuno7, M. Agulnik8

Author affiliations

  • 1 Hematology/ Oncology, Siteman Cancer Center at Barnes-Jewish Hospital and Washington University, 63110 - St. Louis/US
  • 2 Hematology/oncology, Northwestern University, IL 60611 - Chicago/US
  • 3 Medicine, University of Iowa, Iowa City/US
  • 4 Oncology, Mayo Clinic, Jacksonville/US
  • 5 Division Of Medical Oncology, Mayo Clinic, 55905 - Rochester/US
  • 6 Preventive Medicine, Northwestern University, Chicago/US
  • 7 Oncology, Mayo Clinic, 55905 - Rochester/US
  • 8 Hematology/ Oncology, Northwestern University, 60611 - Chicago/US


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Abstract 4770


Topotecan and pazopanib individually have clinical benefit in patients with sarcomas. Pazopanib is a multi-tyrosine kinase inhibitor and topotecan affects endothelial cells, and inhibits HIF-1, an upstream regulator of VEGF expression. The utilization of pazopanib with topotecan is anticipated to produce anti-tumor synergism in patients with osteosarcomas.


A phase II study of pazopanib/topotecan in patients with metastatic and non-resectable osteosarcomas was conducted by the Midwest Sarcoma Trials Partnership. Age >18, ECOG ≤1, adequate organ function, measurable disease and 1 prior therapy were required. Patients were treated with pazopanib 800mg oral daily, Topotecan 8mg orally day 1, 8, 15 on a 28-day cycle until disease progression or unacceptable toxicity. Primary endpoint: progression-free rate (PFR) at 12 weeks. Secondary endpoints: overall response rate (ORR), clinical benefit rate (CBR), OS, median progression free survival (PFS), and 3, and safety and tolerability. Lab correlates evaluated PFR and OS to levels of VEGFR2 and PDGF. Simon 2-stage design was used.


A total of 21 pts were enrolled at 6 sites, with 17 evaluable for response. Mean age was 41 years, 48% of patients were female and 95% had metastatic disease. PFR at 12 weeks is 59% with a median PFS of 4.5 months and OS of 11.1 months. ORR is 6 % and CBR is 85%. Grade 3-4 adverse events (%): neutropenia (42), thrombocytopenia (29), hypertension (16) and anemia (12). Correlative data will be presented.


The combination of pazopanib/topotecan proved extremely promising for patients with unresectable or metastatic osteosarcoma. To date 10 patients have met the primary endpoint. If an anticipate 11 or more patients/ 36 will have disease control at 4 months, the agent would be considered sufficiently efficacious for additional study.

Clinical trial identification


Legal entity responsible for the study

Northwestern University.



Editorial Acknowledgement


M. Agulnik: Advisory board: Novartis. All other authors have declared no conflicts of interest.

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