Open AccessActivity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion
Author(s) -
Vivek Subbiah,
Oliver Holmes,
Kyle Gowen,
Daniel Spritz,
Behrang Amini,
Wei Lien Wang,
Alexa B. Schrock,
Funda MericBernstam,
Ralph Zinner,
Sarina A. Piha-Paul,
Maria A. Zarzour,
Julia A. Elvin,
Rachel Erlich,
David L. Stockman,
Jo Anne Vergilio,
James Suh,
Philip J. Stephens,
Vincent A. Miller,
Jeffrey S. Ross,
Siraj M. Ali
Publication year - 2016
Publication title -
oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.987
H-Index - 98
eISSN - 1423-0232
pISSN - 0030-2414
DOI - 10.1159/000449204
Subject(s) - crizotinib , pazopanib , neurofibromatosis , medicine , cancer research , oncology , pathology , cancer , sunitinib , lung cancer , malignant pleural effusion
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.