Long-term survival of participants in the PASART-1 and PASART-2 trials of neo-adjuvant pazopanib and radiotherapy in soft tissue sarcoma

Authors

  • Bauke H.G. van Riet Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0000-0003-3606-8544
  • Milan van Meekeren Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands https://orcid.org/0000-0001-6934-8652
  • Marta Fiocco Department of Biomedical Data Science, section Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; Mathematical Institute, Leiden University, Leiden, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands https://orcid.org/0000-0001-5588-0277
  • Aisha Miah Department of Clinical Oncology, The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom
  • Ilse de Pree Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands
  • Lisette M. Wiltink Department of Radiotherapy, Leiden University Medical Center, Leiden, the Netherlands https://orcid.org/0000-0003-3483-4241
  • Astrid Scholten Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0000-0002-3242-4989
  • Lotte Heimans Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands https://orcid.org/0000-0002-1735-2307
  • Judith V.M.G. Bovée Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands https://orcid.org/0000-0003-1155-0481
  • Hans Gelderblom Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands https://orcid.org/0000-0001-9270-8636
  • Neeltje Steeghs Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands https://orcid.org/0000-0003-2989-2279
  • Rick L. Haas Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands: Department of Radiotherapy, Leiden University Medical Center, Leiden, the Netherlands https://orcid.org/0000-0003-4834-4331

DOI:

https://doi.org/10.2340/1651-226X.2025.42333

Keywords:

Pre-operative, chemoradiotherapy, soft-tissue sarcoma, pazopanib

Abstract

Objective: This study aims to assess the long-term safety and efficacy of adding pazopanib to neo-adjuvant radiotherapy followed by surgery in patients with high-risk non-metastatic soft tissue sarcoma of the trunk and extremities treated in the PASART-1 and PASART-2 trials, as well as to compare the PASART cohorts to a control cohort receiving standard treatment during the same time period from the Netherlands Cancer Registry (IKNL) to investigate if adding pazopanib improves Overall Survival (OS).

Methods: Updated follow-up data on disease control, survival and long-term toxicities of the PASART-trials were extracted from electronic patient records. The effect of adding pazopanib to neo-adjuvant radiotherapy on OS was investigated by comparing the combined PASART cohorts to the IKNL cohort via direct comparison and exact matching analysis.

Results: PASART-trials included 34 patients, IKNL cohort included 487 patients. After a median follow-up of 75.4 months (range: 30–131 months) the 1-year, 2-year and 5-year OS in the PASART-trials were 97% (95% confidence interval [CI]: 91.5–100), 85.3% (95% CI: 74.2–98.1), 79.3% (95% CI: 66.8–94.2), respectively. Matching resulted in 23 PASART and 89 IKNL patients. Adding pazopanib did not significantly improve OS when compared to standard treatment (IKNL) in a direct comparison (hazard ratio [HR]: 0.58; 95% CI: 0.30–1.13) or matched analysis (HR: 0.70; 95% CI: 0.29–1.73). Long-term toxicities, mainly fibrosis (n = 6) and edema (n = 2), were observed in 11 PASART patients and comparable to historical controls.

Interpretation: The addition of pazopanib had tolerable long-term toxicity but did not improve OS when compared to a control cohort receiving standard treatment.

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2025-01-15

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van Riet, B. H., van Meekeren, M., Fiocco, M., Miah, A., de Pree, I., Wiltink, L. M., … Haas, R. L. (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 Oncologica, 64, 69–77. https://doi.org/10.2340/1651-226X.2025.42333

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Vol. 64 (2025): Acta Oncologica

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Copyright (c) 2025 Bauke H.G. van Riet, Milan van Meekeren, Marta Fiocco, Aisha Miah, Ilse de Pree, Lisette M. Wiltink, Astrid Scholten, Lotte Heimans, Judith V.M.G. Bovée, Hans Gelderblom, Neeltje Steeghs, Rick L. Haas

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