Patrick Schöffski1, Jean-Yves Blay2, Isabelle Ray-Coquard3. 1. Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. 2. Centre Léon Bérard, Unicancer, LYRICAN and Université Claude Bernard Lyon 1. 3. GINECO and Medical Oncology Department, Centre Léon Bérard, Université Claude Bernard Lyon, Lyon, France.
Abstract
PURPOSE OF REVIEW: Sarcomas are a diverse group of rare solid tumors with limited treatment options for patients with advanced, inoperable disease. Cabozantinib is a tyrosine kinase inhibitor currently approved for advanced renal cell, hepatocellular, and medullary thyroid carcinoma. Cabozantinib has potent activity against a variety of kinases, including MET, vascular endothelial growth factor receptor, and AXL, that are associated with sarcoma growth and development. Here we review the preclinical findings and clinical development of cabozantinib in the treatment of soft tissue sarcoma, gastrointestinal stromal tumors (GIST), osteosarcoma, and Ewing sarcoma. RECENT FINDINGS: In vitro, cabozantinib has shown relevant activity in inhibiting the growth and viability of soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma tumor cell lines. Cabozantinib also promoted the regression of GIST in various murine xenografts, including imatinib-resistant models. More than 10 prospective trials with cabozantinib that included patients with sarcomas have been completed or are currently ongoing. Clinical activity with cabozantinib has been recently reported in phase 2 clinical trials for patients with GIST and for patients with osteosarcoma or Ewing sarcoma. SUMMARY: Cabozantinib has shown promising activity for the treatment of various sarcomas, supporting further evaluation in this setting.
PURPOSE OF REVIEW: Sarcomas are a diverse group of rare solid tumors with limited treatment options for patients with advanced, inoperable disease. Cabozantinib is a tyrosine kinase inhibitor currently approved for advanced renal cell, hepatocellular, and medullary thyroid carcinoma. Cabozantinib has potent activity against a variety of kinases, including MET, vascular endothelial growth factor receptor, and AXL, that are associated with sarcoma growth and development. Here we review the preclinical findings and clinical development of cabozantinib in the treatment of soft tissue sarcoma, gastrointestinal stromal tumors (GIST), osteosarcoma, and Ewing sarcoma. RECENT FINDINGS: In vitro, cabozantinib has shown relevant activity in inhibiting the growth and viability of soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma tumor cell lines. Cabozantinib also promoted the regression of GIST in various murine xenografts, including imatinib-resistant models. More than 10 prospective trials with cabozantinib that included patients with sarcomas have been completed or are currently ongoing. Clinical activity with cabozantinib has been recently reported in phase 2 clinical trials for patients with GIST and for patients with osteosarcoma or Ewing sarcoma. SUMMARY:Cabozantinib has shown promising activity for the treatment of various sarcomas, supporting further evaluation in this setting.
Authors: Geraldine O'Sullivan Coyne; Shivaani Kummar; James Hu; Kristen Ganjoo; Warren A Chow; Khanh T Do; Jennifer Zlott; Ashley Bruns; Lawrence Rubinstein; Jared C Foster; Lamin Juwara; Robert Meehan; Richard Piekarz; Howard Streicher; Elad Sharon; Naoko Takebe; Andrea Regier Voth; Donald Bottaro; Rene Costello; John J Wright; James H Doroshow; Alice P Chen Journal: Clin Cancer Res Date: 2021-10-29 Impact factor: 13.801