title: Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.
abstract: Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies. The Children's Oncology Group (COG), in partnership with the National Cancer Institute (NCI), is planning a trial entitled the COG-NCI Pediatric Molecular Analysis for Therapeutic Choice (Pediatric MATCH) protocol utilizing an umbrella design. This protocol will have centralized infrastructure and will consist of a biomarker profiling protocol and multiple single-arm phase II trials of targeted therapies. Pediatric patients with recurrent or refractory solid tumors, lymphomas, or histiocytoses with measurable disease will be eligible. The Pediatric MATCH Target and Agent Prioritization (TAP) committee includes membership representing COG disease committees, the Food and Drug Administration, and the NCI. The TAP Committee systematically reviewed target and agent pairs for inclusion in the Pediatric MATCH trial. Fifteen drug-target pairs were reviewed by the TAP Committee, with seven recommended for further development as initial arms of the Pediatric MATCH trial. The current evidence for availability, efficacy, and safety of targeted agents in children for each class of mutation considered for inclusion in the Pediatric MATCH trial is discussed in this review.
authors.affiliation: Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX, USA.|Division of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health, Dallas, TX, USA.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Laetsch
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Rajen
authors.initials: R
authors.lastname: Mody
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Irwin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lim
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
authors.affiliation: Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
authors.forename: Nita L
authors.initials: NL
authors.lastname: Seibel
authors.affiliation: Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX, USA.|Division of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
authors.affiliation: Division of Pediatric Neurology, Doernbecher Children's Hospital, Portland, OR, USA.|Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Y Jae
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer Center and Blood Disorder Center, Boston, MA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Janeway
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D012107:Research Design; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D015513:Oncogene Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D017468:Receptors, Fibroblast Growth Factor; C065400:oncogene protein trk; C546842:MTOR protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D058570:TOR Serine-Threonine Kinases; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D020930:MAP Kinase Kinase Kinases