2019 ASCO: Nearly One-Quarter of Participants in the Pediatric MATCH Trial Have an Actionable Molecular Alteration


Key Points

  • Approximately 25% of the patients enrolled in the Pediatric MATCH trial have tumors with targetable molecular alterations and have been assigned to a phase II arm of molecularly targeted therapies.
  • The collaborative nationwide study is facilitating the evaluation of molecularly targeted agents in pediatric patients with actionable molecular alterations in their tumors.

A study investigating the frequency of targetable molecular alterations in pediatric cancer among patients enrolled in the National Cancer Institute–Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) trial has found that about one-quarter of patients with tumors submitted for screening have a targetable molecular alteration. The study by Parsons et al will be presented during the 2019 ASCO Annual Meeting (Abstract 10011).

Pediatric MATCH Criteria

Patients aged 1–21 years with treatment-refractory or recurrent solid tumor cancers, non-Hodgkin lymphomas, or histiocytic disorders treated at U.S.-based Children’s Oncology Group trial sites are eligible to participate in the Pediatric MATCH trial. The screening protocol for the MATCH trial detects tumor alterations that are used to assign patients with treatment-refractory or recurrent cancers to phase II treatment arms of molecularly targeted therapies. 

DNA and RNA are extracted from formalin-fixed paraffin-embedded tumor samples and sequenced using an Oncomine cancer gene panel for detection of gene mutations, amplifications, and fusions. Loss of SMARCB1, SMARCA4, and PTEN expression is detected by immunohistochemistry. Lists of actionable mutations based on available clinical and preclinical data are used a priori to determine eligibility for treatment arms.

Study Results

Between July 2017 and December 2018, researchers enrolled 422 patients with a median age of 13 years in the trial. Solid tumor cancers comprised 71% (n = 300) of diagnoses, central nervous system tumors comprised 24% (n = 101) of diagnoses, and lymphomas/histiocytosis comprised 5% (n = 21) of diagnoses. A tumor sample was submitted for 390 patients; sequencing was attempted for 370 (95%) patients; and results were confirmed for 357 (92%) patients.

An actionable mutation for at least one of the 10 current treatment arms was identified in 112 patients (29%, 95% confidence interval [CI] = 24%–33%); 95 patients (24%, 95% CI = 20–29%) were assigned to a treatment arm, with 39 patients (10%, 95% CI = 7%–13%) enrolled to date. The actionable mutation rate was similar in patients less than 12 years old (35%) compared to patients aged 12 years and older (25%). 

Actionable MAPK pathway alterations were found in 11% of the patients (n = 41), most often HRAS/KRAS/NRAS mutations (n = 16), BRAF mutations or fusions (n = 14), or NF1 mutations (n = 11). Other genes with recurrent actionable mutations included SMARCB1 (n = 14), ALK (n = 8), CDK4 (n = 8), PIK3CA (n = 7), PTEN (n = 7), FGFR1 (n = 5), and BRCA1/BRCA2 (n = 5).

“Approximately one-quarter of patients with tumors submitted for Pediatric MATCH screening have been assigned to an investigational therapy, facilitating the evaluation of molecularly targeted agents in biomarker-positive pediatric cohorts through a collaborative nationwide study,” concluded the study authors.

“Our study shows that we can successfully create a nationwide molecular screening trial for children, adolescents, and young adults with cancers that have been resistant to treatment,” said study author Will Parsons, MD, PhD, Associate Professor of Pediatrics/Oncology at Baylor College of Medicine. “One of our key goals has been to expand access to targeted therapies for pediatric [patients with] cancer across the country, and these early results suggest that goal is within reach.”

Disclosure: Funding for this study was provided by the National Institutes of Health. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.