Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.
Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.
The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.
Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.
He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?
The Pediatric MATCH trial () was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.
After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:
- larotrectinib (targeting NTRK fusions).
- erdafitinib (targeting FGFR1/2/3/4).
- tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
- LY3023414 (targeting the PI3K/MTOR pathway).
- selumetinib (targeting the MAPK pathway).
- ensartinib (targeting ALK or ROS1).
- vemurafenib (targeting BRAF V600 mutations).
- olaparib (targeting defects in DNA damage repair).
- palbociclib (targeting alterations in cell cycle genes).
- ulixertinib (targeting MAPK pathway mutations).
From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.
The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).
A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.
“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.
Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.
Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.
“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”
The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.
SOURCE: Parsons DW et al. ASCO 2019,