Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas
| Autor: | Robert S. Meehan, Ashley Bruns, Lamin Jawara, Geraldine O'Sullivan Coyne, James C. Hu, Naoko Takebe, Alice P. Chen, S. Kummar, Andrea Regier Voth, Jared C. Foster, Howard Streicher, Kristen N. Ganjoo, Khanh T. Do, Rene Costello, Elad Sharon, Jennifer Zlott, Larry Rubinstein, Donald P. Bottaro, Warren A. Chow, John Wright, Richard Piekarz, James H. Doroshow |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research, vol 28, iss 2 Clin Cancer Res |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|