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Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas
- Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research, vol 28, iss 2, Clin Cancer Res
- Publication Year :
- 2021
- Publisher :
- American Association for Cancer Research (AACR), 2021.
-
Abstract
- Purpose: Soft-tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated vascular endothelial growth factor (VEGF) levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population. Patients and Methods: We performed an open-label, multi-institution, single-arm phase II trial of single-agent cabozantinib in adult patients with advanced STS and progressive disease after at least 1 standard line of systemic therapy. Patients received 60 mg oral cabozantinib once daily in 28-day cycles, and dual primary endpoints of overall response rate and 6-month progression-free survival (PFS) were assessed. Changes in several circulating biomarkers were assessed as secondary endpoints. Results: Six (11.1%; 95% CI, 4.2%–22.6%) of the 54 evaluable patients enrolled experienced objective responses (all partial responses). Six-month PFS was 49.3% (95% CI, 36.2%–67.3%), with a median time on study of 4 cycles (range, 1–99). The most common grade 3/4 adverse events were hypertension (7.4%) and neutropenia (16.7%). Patients' levels of circulating hepatocyte growth factor (HGF), soluble MET, and VEGF-A generally increased after a cycle of therapy, while soluble VEGFR2 levels decreased, regardless of clinical outcome. Conclusions: Cabozantinib single-agent antitumor activity was observed in patients with selected STS histologic subtypes (alveolar soft-part sarcoma, undifferentiated pleomorphic sarcoma, extraskeletal myxoid chondrosarcoma, and leiomyosarcoma) highlighting the biomolecular diversity of STS.
- Subjects :
- Vascular Endothelial Growth Factor A
Oncology
Cancer Research
medicine.medical_specialty
Cabozantinib
Pyridines
medicine.drug_class
Clinical Trials and Supportive Activities
Oncology and Carcinogenesis
Population
Neutropenia
Article
Tyrosine-kinase inhibitor
chemistry.chemical_compound
Rare Diseases
Clinical Research
Internal medicine
Alveolar soft part sarcoma
medicine
Humans
Anilides
Oncology & Carcinogenesis
Progression-free survival
education
Protein Kinase Inhibitors
Cancer
education.field_of_study
business.industry
Evaluation of treatments and therapeutic interventions
Sarcoma
medicine.disease
chemistry
6.1 Pharmaceuticals
business
Progressive disease
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....2cf81dcbb45f55e902cc6a8bdce4a27b
- Full Text :
- https://doi.org/10.1158/1078-0432.ccr-21-2480