Factors impacting enrollment on NCI-COG Pediatric MATCH trial treatment protocols.
Authors: Parsons Donald Williams , Janeway Katherine A. , Patton David R , Lee Jennifer , Coffey Brent , Williams Paul M. , Roy-Chowdhuri Sinchita , Tsongalis Gregory J. , Routbort Mark , Ramirez Nilsa C. , Saguilig Lauren , Piao Jin , Alonzo Todd Allen , Berg Stacey L. , Fox Elizabeth , Hawkins Douglas S. , Mooney Margaret M. , Takebe Naoko , Tricoli James V. , Seibel Nita ,   The NCI-COG Pediatric MATCH Team
Published: June 2021

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Background: The NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial assigns patients age 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on the genetic alterations detected in their tumor. Treatment arm assignments and enrollment decisions have now been made for 1000 study participants: we report here match and enrollment data and factors affecting treatment protocol enrollment. Methods: Patients enrolled in the Pediatric MATCH screening protocol were assigned to an open treatment protocol if an actionable mutation (aMOI) was detected by tumor DNA and RNA-based cancer gene panel sequencing. After a match, treatment protocol enrollment must occur within 8-12 weeks. Patient demographic data, reasons for not enrolling on treatment protocol (if applicable), and prior history of molecular testing were reported by study sites. The Fisher exact test was used to compare protocol enrollment rates between groups. Results: Results were analyzed for the first 1000 patients with testing completed (enrolled between July 2017 and October 2020). At least one tumor aMOI was detected in 310 (31%) patients and treatment protocol slots were available for 284 patients (28%). A total of 131 patients (46% of those matched) enrolled on a treatment arm. No difference in treatment protocol match or enrollment rate was observed for gender, race, or ethnicity. Both treatment protocol match rate (105/275, 38% vs 86/394, 22%) and enrollment rate (56/275, 20% vs 33/394, 8%) were significantly more frequent in patients with a reported history of prior molecular testing (p<0.0001). The most common reasons provided for not enrolling on a treatment protocol were: patient receiving other treatment (32% of responses), poor clinical status (16%), lack of measurable disease (11%), or ineligible diagnosis for that treatment arm (10%). Ineligibility due to history of excluded prior targeted therapy (6%) or inability to swallow capsules (4%) was less frequent. Conclusions: The rate of Pediatric MATCH treatment protocol enrollment has exceeded pre-study projections, due to more frequent actionable mutation detection and treatment assignment than anticipated (28% observed, 10% projected). This may in part reflect an increased number of targetable events in recurrent or refractory pediatric cancers. Correlative studies analyzing pre-treatment tumors from MATCH study patients are underway and will address this hypothesis. Prior history of molecular testing was associated with higher match and enrollment rate and poor clinical status was a common reason for not enrolling on a treatment protocol, suggesting that early molecular screening of children with solid malignancies may facilitate enrollment to biomarker-selected trials of targeted therapies. Clinical trial information: NCT03155620.