Early Findings on EZH2 Inhibitor in Children With Rare Solid Tumors


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Susan N. Chi, MD

Susan N. Chi, MD

CHILDREN WITH relapsed or refractory malignant rhabdoid tumors, epithelioid sarcomas, or poorly differentiated chordomas with a particular genetic defect were treated with the investigational drug tazemetostat and appeared to tolerate treatment well. Some patients had objective and durable responses, according to data from a phase I clinical trial, EZH-102,1 presented by Susan N. Chi, MD, Director of the Pediatric Brain Tumor Clinical Trials Program and Assistant Professor in Pediatric Neuro-oncology at Dana-Farber Cancer Institute and Boston Children’s Hospital, at the American Association for Cancer Research–National Cancer Institute–European Organisation for Research and Treatment of Cancer (AACR-NCI-EORTC) International Conference on Molecular Targets and Cancer Therapeutics. 

Tazemetostat, a potent and selective EZH2 inhibitor, is generally well tolerated in children and showed antitumor activity, including complete responses in patients with INI1-negative tumors. INI1 is a gene that is uniquely mutated in these types of tumors, Dr. Chi said. This mutation leads to deficiencies in DNA transcription and cell proliferation, so cancer cells use an alternate pathway to enable proliferation. The protein EZH2 is a component of this alternate pathway. Tazemetostat targets EZH2, thus inhibiting the proliferative activity of cancer cells, she explained. 

Dr. Chi and colleagues enrolled patients from 6 months to 21 years old with INI1-negative tumors in this multicenter study. Of the 46 patients treated so far, 3 had complete responses, and 1 patient with poorly differentiated chordoma had a partial response. Adverse events were generally mild to moderate. 

DISCLOSURE: Dr. Chi reported no conflicts of interest. 

REFERENCE 

1. Chi S, et al: 2017 AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics. Abstract A175. Presented October 28, 2017. 


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