Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology

J Surg Oncol. 2023 Apr;127(5):871-881. doi: 10.1002/jso.27205. Epub 2023 Feb 13.

Abstract

Background and objectives: The impact upon wound healing of targeted molecular therapies, when incorporated into neoadjuvant therapy of soft tissue sarcoma, is largely unknown. Here, we describe wound complications following addition of pazopanib, a tyrosine kinase inhibitor (TKI), to neoadjuvant radiotherapy (RT) +/- chemotherapy for soft tissue sarcoma.

Methods: Wound complications were evaluated on dose-finding and randomized arms of ARST1321, a phase II/III study incorporating neoadjuvant RT, +/- pazopanib, +/- ifosfamide/doxorubicin (ID) for sarcoma therapy.

Results: Of 85 evaluable patients, 35 (41%) experienced postoperative wound complications. Most (57%) were grade III. Randomization to pazopanib + RT + ID carried a 50% wound complication rate (17/34, with 47% grade III), compared to 22% (5/23) with ID + RT alone. In nonchemotherapy study arms, pazopanib + RT resulted in a 59% wound complication rate versus 25% for those receiving RT alone. Grade III wound complications occurred among 26% (15/58) of all patients receiving pazopanib. Wound complications occurred a median of 35 days postoperatively. Some occurred following diagnostic biopsies and at remote surgical sites.

Conclusion: The addition of pazopanib to neoadjuvant chemotherapy and RT resulted in a higher wound complication rate following therapy of soft tissue sarcoma. The rate of grade III complications remained comparable to that reported in contemporary literature.

Keywords: neoadjuvant; pazopanib; sarcoma; wound complications; wound healing.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Child
  • Humans
  • Neoadjuvant Therapy / adverse effects
  • Neoadjuvant Therapy / methods
  • Postoperative Complications / etiology
  • Pyrimidines / adverse effects
  • Sarcoma* / pathology
  • Soft Tissue Neoplasms* / pathology

Substances

  • pazopanib
  • Pyrimidines