# Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial

Source: https://onco.cc/key-papers/paper-eckstein-j-clin-oncol/  
OnCo record `paper-eckstein-j-clin-oncol` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one trial page, indexed on Europe PMC as PubMed record 35363510 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.

## Summary

Purpose: The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib.

Methods: Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib.

Results: Twenty patients (median age: 14 years) were treated. All were evaluable for response and toxicities. The most frequent diagnoses were high-grade glioma (HGG; n = 7) and rhabdomyosarcoma (n = 7). Twenty-one actionable mutations were detected: hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), inactivating mutations in NF1 (n = 7), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease including two patients with HGG ( NF1 mutation, six cycles; KRAS mutation, 12 cycles). Six-month progression-free survival was 15% (95% CI, 4 to 34). Five patients (25%) experienced a grade 3 or higher adverse event that was possibly or probably attributable to study drug.

Conclusion: A national histology-agnostic molecular screening strategy was effective at identifying children and young adults eligible for treatment with selumetinib in the first Pediatric MATCH treatment arm to be completed. MEK inhibitors have demonstrated promising responses in some pediatric tumors (eg, low-grade glioma and plexiform neurofibroma). However, selumetinib in this cohort with treatment-refractory tumors harboring MAPK alterations demonstrated limited efficacy, indicating that pathway mutation status alone is insufficient to predict response to selumetinib monotherapy for pediatric cancers.

Indexed on Europe PMC as PubMed record 35363510 (DOI 10.1200/jco.21.02840). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Journal of Clinical Oncology
- Year: 2022
- DOI: 10.1200/jco.21.02840
- Authors: Eckstein OS, Allen CE, Williams PM, et al.
- What it means: One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- J Clin Oncol 2022: https://doi.org/10.1200/jco.21.02840
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35363510/
- Europe PMC: https://europepmc.org/article/MED/35363510

## Connected records

- trials: [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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