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The Pediatric MATCH Study: Actionable Targets Found in 25% of Young Patients with Cancer

TON - October 2019, Vol 12, No 5 - Pediatric Cancer
Wayne Kuznar

Chicago, IL—Approximately 25% of children, adolescents, and young adults with advanced cancer were eligible for a targeted therapy after genotyping of their tumors in the Pediatric Molecular Analysis for Therapy Choice (MATCH) clinical trial. That rate is more than double the 10% that researchers had projected.

The Pediatric MATCH study was developed and is led jointly by the National Cancer Institute (NCI) and the Children’s Oncology Group (COG), and is the first nationwide study focusing on precision medicine in pediatric patients with cancer. Will Parsons, MD, PhD, Deputy Director, Texas Children’s Cancer and Hematology Centers, Baylor College of Medicine, Houston, presented the findings at ASCO 2019.

“This study is allowing us to evaluate targeted therapies in patients with many different cancer types—some common, some rare—so hopefully we can effectively study these agents and identify signals of activity where some of these drugs may work for our patients,” said Dr Parsons.

The Pediatric MATCH study was launched in 2017 to identify specific genetic alterations in young patients with cancers that have not responded to standard treatment. Patients are enrolled in a screening protocol in which their tumors are sequenced. If a treatment matched to any genetic alteration is found, the patient is offered enrollment into a Pediatric MATCH phase 2 treatment clinical trial. Currently, there are 10 active phase 2 clinical trials, 1 for each single-agent targeted drug being tested. An additional 4 targeted agents are in development, Dr Parsons said.

Patients eligible for the screening protocol were between ages 1 and 21 years (median age, 13 years), with a diagnosis of recurrent or refractory solid tumors. The treatment subprotocol calls for the presence of a defined actionable mutation for that treatment arm.

By the end of 2018, 422 patients from 93 sites had been enrolled in the screening protocol, and tumor samples were received for 357 (92%) patients, accounting for more than 60 tumor types. Among the various diagnoses, 24% were central nervous system (CNS) tumors, 71% were non-CNS solid tumors, and 5% were lymphomas and histiocytoses.

Overall, 29% of the patients had an actionable mutation detected, and a treatment was assigned to 24% of patients. The most common alterations were RAS mutations, BRAF mutations or fusions, SMARCB1 mutations or deletions, and NF1 mutations.

To date, a total of 41% of patients who have been matched have been enrolled in a phase 2 clinical trial, Dr Parsons said, “and that’s a number that will be expected to continue to increase slightly as patients who are matched are still eligible to be treated on those protocols.”

The median time from tumor sample receipt to treatment assignment is 15 days. The match rate so far was 46% for CNS tumors and 26% for non-CNS tumors.

The non-CNS tumors ranged from 13% for osteosarcoma to more than 50% for rhabdomyosarcoma, representing “an appreciable detection rate across the diversity of common non-CNS tumors,” said Dr Parsons. Actionable mutations for CNS tumors were driven largely by the predominance of high-grade and low-grade astrocytomas. An actionable mutation was detected in 29 of 39 (74%) astrocytomas.

“Patients with astrocytoma have been matched to 9 of the 10 available matched treatment protocols,” Dr Parsons added.

“Our initial experience has demonstrated that the collaborative NCI-COG Pediatric MATCH has been successfully able to create a framework in which we can efficiently collect, process, sequence, and assign patients to treatments in a nationwide clinical trial,” he concluded.

ASCO President Monica M. Bertagnolli, MD, FACS, FASCO, Chief, Division of Surgical Oncology, Brigham and Women’s Hospital, Boston, highlighted the potential impact of the study findings on the introduction of precision medicine into the pediatric cancer treatment landscape.

“Today we cure a large number of children with cancer, but there are still many patients needing better treatments,” Dr Bertagnolli said. “These results bring us one step closer to bringing the precision medicine era to pediatric cancer care. Now that we know that targetable genetic alterations are fairly common in pediatric cancers, we have an exciting opportunity to boost success rates,” she added.

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Last modified: October 7, 2019