{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:03:19Z","timestamp":1783335799854,"version":"3.54.6"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The National Cancer Institute-Children\u2019s Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1\/2, RAD51C\/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg\/m2\/dose. Two participants were fully evaluable; 4 were inevaluable because &amp;lt;85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                  <jats:p>NCT03233204. IRB approved: initial July 24, 2017.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae096","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T20:40:25Z","timestamp":1717101625000},"page":"638-e952","source":"Crossref","is-referenced-by-count":9,"title":["Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5316-6440","authenticated-orcid":false,"given":"Julia L","family":"Glade Bender","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center , New York, NY , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerice","family":"Pinkney","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Memorial Regional Hospital\/Joe Dimaggio Children\u2019s Hospital , Hollywood, FL , United 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Monrovia, CA , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A","family":"Alonzo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Keck School of Medicine, University of Southern California , Los Angeles, CA , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey L","family":"Berg","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Cancer and Hematology Center, Baylor College of Medicine , Houston, TX , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilsa C","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Biopathology Center, Nationwide Children\u2019s Hospital , Columbus, OH , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Oncology, St Jude Children\u2019s Research Hospital , Memphis, TN , United 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