Soft tissue sarcomas are rare malignant tumors of mesenchymal origin, that can arise virtually anywhere in the body. Standard treatment for localized high-risk soft tissue sarcoma is surgery combined with radiotherapy. Pre-operative radiation has a more favorable late toxicity profile compared to post-operative radiotherapy, however at the cost of a higher rate of wound complications (35% vs. 17%). This combined treatment approach has resulted in high local control rates, but the effect on the prevention of distant metastases and on survival parameters is limited, hence the importance of examining other (combinations of) treatment modalities.
Pazopanib is an oral multitarget tyrosine kinase inhibitor (TKI), and its mode of action is suggested to be an interference with angiogenesis by blocking the VEGF-axis. Pazopanib has demonstrated activity in metastatic soft tissue sarcoma and has shown promising results when combined with radiotherapy for several tumor types, with a potential synergistic, radiosensitizing effect.
In the phase 2 PASART-II clinical trial, the efficacy, feasibility and safety of the neo-adjuvant combination of pazopanib and radiotherapy will be examined in high-risk, localized soft tissue sarcoma.
If the results of this trial are positive, oncologists could be provided with a new treatment modality for this rare type of tumours, decreasing treatment side-effects, and improving patient survival and quality of life.
van Riet BHG, van Meekeren M, Fiocco M, Miah A, de Pree I, Wiltink LM, Scholten A, Bovée JVMG, Steeghs N & Haas RL (2025). Long-term survival of participants in the PASART-1 and PASART-2 trials of neo-adjuvant pazopanib and radiotherapy in soft tissue sarcoma. Acta Oncol, 64:69-77. doi: 10.2340/1651-226X.2025.42333
van Meekeren M, Bovee JVMG, van Coevorden F, van Houdt W, Schrage Y, Koenen AM, Miah AB, Zaidi S, Hayes AJ, Thway K, Krolh S, Fiocco M, Gelderblom H, Steeghs N & Haas RL (2021). A phase II study on the neo-adjuvant combination of pazopanib and radiotherapy in patients with high-risk, localized soft tissue sarcoma. Acta Oncol, 60(12):1557-1564. doi: 10.1080/0284186X.2021.1971294
Prof.dr. M. Fiocco, Mathematical Institute Leiden University, Department of Biomedical Data Sciences Leiden University Medical Center & Princess Máxima Center for Pediatric Oncology
Prof.dr. H. Gelderblom, Department of Medical Oncology at the Leiden University Medical Centre
Prof.dr. R. L. M. Haas, MD, Department of Radiotherapy, Leiden University Medical Center & The Netherlands Cancer Institute
Dr. Neeltje Steeghs, MD, The Netherlands Cancer Institute
M. van Meekeren, MD, Department of Radiotherapy, Leiden University Medical Center & The Netherlands Cancer Institute