PFS Improvement Demonstrated With a Multinational Pediatric Cancer Registry in High-Risk Patients


"This is the first time that such a large precision oncology platform [involving] pediatric patients was assessed for its clinical benefit."

Cornelis M. van Tilburg, MD, PhD

For adult malignancies, potential therapeutic targets are identified using real-time comprehensive profiling, which provides valuable diagnostic information. For pediatric patients, however, the process is underutilized, which leaves a siginificant unmet need. With the INFORM (INdividualized therapy FOr Relapsed Malignancies in Childhood) registry, investigators in Heidelberg, Germany showed the utility of applying a large-scale multinational personalized oncology platform in decision-making to improve clinical benefit. Diagnostic refinement and targeted therapy options to pediatric patients was also provided with INFORM.

“This is the first time that such a large precision oncology platform [involving] pediatric patients was assessed for its clinical benefit,” Cornelis M. van Tilburg, MD, PhD, senior physician in Pediatric Oncology and Hematology, and head, Early Phase Clinical Trials at the Hopp Children's Cancer Center, in Heidelberg, Germany, said during a press program ahead of the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.1

Eight countries participated in the study by sending samples from pediatric patients for molecular analysis. The analyses were shared with an online interdisciplinary molecular tumor board that included the patient’s pediatric oncologist. A predefined algorithm using a 7-step scale that ranged from “very high priority” to “very low priority” target labels was implemented and was based on how druggable the target was, the alteration type, and any specific evidence. Treating physicians could access an online database to review the analyses.

“It is important to note that INFORM is not a clinical trial,” Tilburg said. “Treatment decisions made by the patient’s physician encompassed either enrolling the pediatric patient in a clinical trial, prescribing an off-label targeted drug, or treating with conventional therapy.” Any documentation follow-up was included in the online database.

In the analysis presented at ASCO, samples from 526 children were evaluated, of which 149 received a matching targeted drug. Twenty samples were determined to have the highest priority label. Children with higher-level targets more frequently received a matching targeted drug, said Tilburg. Seventeen children (3.2%) enrolled in clinical trials and 40 children (7.6%) with a potential cancer predisposition syndrome were detected, 17 of which were previously unknown. Families of these children were offered genetic counseling. “In approximately 8% of the brain tumors, we were able to provide diagnostic refinement of the original diagnosis,” Tilburg said.

Progression-free survival (PFS) rates in patients who received a matching targeted drug were similar to patients who did not receive a matching targeted drug. The survival curves overlap, said Tilburg.

An analysis of the highest priority level targets, however, reveals that those patients who had a very high priority level target and received a matching targeted drug had a median PFS rate of 204.5 days, compared with all other children, whose PFS rate was 114.0 days. “Children with very high priority level target show longer PFS,” Tilburg said.

In the initial INFORM study, 214 tumor samples of pediatric patients at high-risk were profiled and collected from 47 German centers.2 A breakdown of tumor types revealed that 39% were sarcomas, 30% were brain tumors, 13% were neuroblastomas, and 18% were hematological or other malignancies. On average, the turnaround time from tissue arrival to molecular results was 21 calendar days. In 14 of 214 patients (7%), the investigators identified an underlying germline predisposition syndrome. The investigators detected 1 or more potentially druggable alterations in 69% of samples (147 out of 214). Based on these findings, targeted therapeutics were incorporated into the therapy regimen in one-third of patients.

Tilburg said that pediatric precision oncology in a real-world, multinational setting is feasible. For the subgroup of children with very high priority level targets, the INFORM registry provided therapeutic opportunities and new diagnostic information.

“Looking to future research, there is an urgent need for biomarker-driven pediatric interventional clinical trials,” Tilburg said. “A significant group of patients didn't have very high-level targets and we should put our efforts in adding additional layers of diagnostics to allow them to benefit from new treatments,” he concluded.


1. Van Tilburg CM. The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups. J Clin Oncol. 2020;38(suppl; abstr LBA10503). doi: 10.1200/JCO.2020.38.15_suppl.LBA10503

2. Worst BC, Pfaff E, Van Tilburg CM, et al. The INFORM personalized medicine study for high-risk pediatric cancer patients. J Clin Oncol. 2017;35(suppl 15):10509-10509. doi: 10.1200/JCO.2017.35.15_suppl.10509

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