Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion.
Oncology
; 91(6): 348-353, 2016.
Article
in En
| MEDLINE
| ID: mdl-27764830
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Neoplasms
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Antineoplastic Combined Chemotherapy Protocols
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Oncogene Proteins, Fusion
/
Neuroectodermal Tumors
/
Intestinal Neoplasms
/
Liver Neoplasms
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Oncology
Year:
2016
Type:
Article
Affiliation country:
United States