Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion
| Autor: | Kyle Gowen, Wei Lien Wang, Jo Anne Vergilio, David L. Stockman, Sarina Anne Piha-Paul, Vincent A. Miller, Vivek Subbiah, Jeffrey S. Ross, Philip J. Stephens, Funda Meric-Bernstam, Daniel Spritz, Maria Alejandra Zarzour, Julia A. Elvin, Ralph Zinner, Oliver Holmes, Behrang Amini, Alexa B. Schrock, James Suh, Rachel L. Erlich, Siraj M. Ali |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Oncology Cancer Research Oncogene Proteins Fusion Pyridines Neuroectodermal Tumors 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Sulfonamides Liver Neoplasms General Medicine Middle Aged Proto-Oncogene Proteins c-met 3. Good health 030220 oncology & carcinogenesis Female Clear-cell sarcoma Sarcoma medicine.drug Adult medicine.medical_specialty Indazoles Adolescent medicine.drug_class Bone Neoplasms Context (language use) Article Pazopanib Young Adult 03 medical and health sciences Crizotinib Internal medicine Intestinal Neoplasms medicine Humans Neuroectodermal tumor Response Evaluation Criteria in Solid Tumors business.industry Receptor Protein-Tyrosine Kinases medicine.disease ALK inhibitor Pyrimidines 030104 developmental biology Pyrazoles business |
| Zdroj: | Oncology. 91:348-353 |
| ISSN: | 1423-0232 0030-2414 |
| Popis: | Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients. Herein, we present a patient with a small bowel GNET who experienced recurrent hepatic and skeletal metastases after a primary resection. Comprehensive genomic profiling (CGP) in the course of clinical care with DNA and RNA sequencing demonstrated the presence of an exon 7 to exon 6 EWSR1-CREB1 fusion in the context of a diploid genome with no other genomic alterations. In a clinical trial, the patient received a combination of 250 mg crizotinib with 600 mg pazopanib quaque die and achieved partial response and durable clinical benefit for over 2.8 years, and with minimal toxicity from therapy. Using a CGP database of over 50,000 samples, we identified 11 additional cases that harbor EWSR1-CREB1 and report clinicopathologic characteristics, as these patients may also benefit from such a regimen. |
| Databáze: | OpenAIRE |
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