Activity of c-Met/ALK Inhibitor Crizilinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EINSR1-CREB1 Fusion

作者：Subbiah Vivek^*; Holmes Oliver; Gowen Kyle; Spritz Daniel; Amini Behrang; Wang Wei Lien; Schrock Alexa B; Meric Bernstam Funda; Zinner Ralph; Piha Paul Sarina; Zarzour Maria; Elvin Julia A; Erlich Rachel L; Stockman David L; Vergilio Jo Anne; Suh James H; Stephens Philip J; Miller Vincent; Ross Jeffrey S; Ali Siraj M

来源：Oncology, 2016, 91(6): 348-353.

DOI：10.1159/000449204

• Case report
• Crizotinib
• Pazopanib
• Gastrointestinal neuroectodermal tumor
• Clear-cell sarcoma
• EWSR1
• CREB1
• Comprehensive genomic profiling
• Genomic profiling

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-ATFI or EWSRI-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.

• 出版日期2016