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Annals of Surgical Oncology

, Volume 26, Issue 5, pp 1332–1339 | Cite as

Preoperative Pazopanib in High-Risk Soft Tissue Sarcoma: Phase II Window-of Opportunity Study of the German Interdisciplinary Sarcoma Group (NOPASS/GISG-04)

  • Ulrich Ronellenfitsch
  • Ioannis Karampinis
  • Antonia Dimitrakopoulou-Strauss
  • Christos Sachpekidis
  • Jens Jakob
  • Bernd Kasper
  • Kai Nowak
  • Lothar Pilz
  • Ulrike Attenberger
  • Timo Gaiser
  • Hans-Günther Derigs
  • Matthias Schwarzbach
  • Peter HohenbergerEmail author
Sarcoma

Abstract

Background

Preoperative devascularization might improve local control and thus the outcome of patients with soft tissue sarcoma (STS). The multikinase inhibitor pazopanib has antiangiogenic effects and is approved for treating metastatic STS. We conducted a trial of preoperative pazopanib therapy in high-risk STS.

Methods

This single-arm, phase II trial included patients with resectable, non-metastatic, treatment-naïve, high-risk STS. Patients received pazopanib 800 mg daily while waiting for surgery (21-day ‘window of opportunity’). The primary endpoint was metabolic response rate (MRR; proportion of patients with ≥ 50% reduction of mean standardized uptake value [SUVmean] in post- vs. pretreatment fluorodeoxyglucose–positron emission tomography/computed tomography [FDG-PET-CT]). Planned sample size was 35 patients (type I error, 5%; type II error, 20%). A translational substudy explored associations between response and concentration of circulating angiogenic factors.

Results

Futility analysis was performed after 21 patients (11 female, mean age 67 years; liposarcoma n = 15); 17/21 patients were evaluable for the primary endpoint. The MRR was 1/17 (5.9%, 95% confidence interval < 0.01–0.29). Mean change in SUVmean of post- versus pretreatment PET was a 6% decrease (range 65% decrease to 34% increase); 7/21 (33.3%) patients had 12 grade 3/4 toxicities, and 19/21 (95.2%) patients were resected (all R0). One (4.8%) patient suffered a grade 4 postoperative complication (anastomotic leakage). Circulating endothelial progenitor cells, soluble vascular endothelial growth factor, and angiopoietin-2 concentrations showed no relevant changes during treatment.

Conclusions

Although this study showed that preoperative pazopanib is not effective for unselected high-risk STS patients, relevant treatment effects were observed in a single patient. Future research needs to better define subgroups potentially benefiting from preoperative pazopanib treatment.

ClinicalTrials.gov identifier

NCT01543802.

Notes

Acknowledgment

This study was partially funded by GlaxoSmithKline Oncology/Novartis. The authors thank the study center of the German Interdisciplinary Sarcoma Group Michaela Sommer and Marion Bergmann PhD for support in planning and conducting the study, and Ms Silke Deiters for assistance in the translational analyses.

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Ulrich Ronellenfitsch
    • 1
    • 2
  • Ioannis Karampinis
    • 2
  • Antonia Dimitrakopoulou-Strauss
    • 3
  • Christos Sachpekidis
    • 3
  • Jens Jakob
    • 2
    • 4
  • Bernd Kasper
    • 5
  • Kai Nowak
    • 2
    • 6
  • Lothar Pilz
    • 7
  • Ulrike Attenberger
    • 8
  • Timo Gaiser
    • 9
  • Hans-Günther Derigs
    • 10
  • Matthias Schwarzbach
    • 11
  • Peter Hohenberger
    • 2
    Email author
  1. 1.Department of Vascular Surgery and Endovascular SurgeryUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Division of Surgical Oncology and Thoracic SurgeryUniversity Medical Center MannheimMannheimGermany
  3. 3.Clinical Cooperation Unit Nuclear MedicineGerman Cancer Research CenterHeidelbergGermany
  4. 4.Department of General, Visceral and Child SurgeryUniversity Medical Center GöttingenGöttingenGermany
  5. 5.Interdisciplinary Tumor Center MannheimSarcoma UnitMannheim University Medical CenterMannheimGermany
  6. 6.Department of Abdominal, Vascular and Thoracic SurgeryRomed KlinikumRosenheimGermany
  7. 7.Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  8. 8.Institute of Clinical Radiology and Nuclear MedicineUniversity Medical Center MannheimMannheimGermany
  9. 9.Institute of PathologyUniversity Medical Center MannheimMannheimGermany
  10. 10.Department of Hematology and OncologyKlinikum Frankfurt-HoechstFrankfurt am MainGermany
  11. 11.Department of SurgeryKlinikum Frankfurt-HoechstFrankfurt am MainGermany

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