The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets

Abstract

INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99-not applicable], compared with 117 days (95% CI, 106-143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases. SIGNIFICANCE: The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes.See related commentary by Eggermont et al., p. 2677.This article is highlighted in the In This Issue feature, p. 2659.

Figure 1.

Patient disposition. ^aRegistered after October 1, 2017, and still alive and with ongoing follow-up (because regular follow-up of 2 years not complete) at the data cutoff. ^bAt least 2 years of regular follow-up completed, lost to follow-up, or deceased. This includes patients registered after October 1, 2017, who were lost to follow-up or deceased.

Figure 2.

Distribution of the highest priority level target per patient over diagnoses. For each patient, only the highest priority level target is included. ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ATRT, atypical teratoid rhabdoid tumor; DSRCT, desmoplastic round cell tumor; EPN, ependymoma; EWS, Ewing sarcoma; HGG, high-grade glioma (including diffuse-intrinsic pontine glioma); MB, medulloblastoma; MRT, malignant rhabdoid tumor; NB, neuroblastoma; NHL, non-Hodgkin lymphoma; OS, osteosarcoma; other heme, other hematologic malignancies; RMS, rhabdomyosarcoma; STS, soft-tissue sarcoma. *, Including four patients with a target not matching one of the priority levels.

Figure 3.

Survival analyses. A, PFS of patients separated by application of matching targeted drug versus all other patients (P = 0.967). B, OS of patients separated by application of matching targeted drug versus all other patients (P = 0.144). C, PFS of patients separated by application of matching targeted drug in very high priority level patients versus all other patients (P = 0.011). D, OS of patients separated by application of matching targeted drug in very high priority level patients versus all other patients (P = 0.32). E, PFS of patients separated by application of matching targeted drug for very high priority level patients versus very high priority level patients who did not receive matching target drugs versus all other patients (P = 0.034). F, OS of patients separated by application of matching targeted drug for very high priority level patients versus very high priority level patients who did not receive matching target drugs versus all other patients (P = 0.518). G, PFS of patients separated by application of matching targeted drug for very high priority level patients versus high, moderate, and intermediate level patients versus borderline, low, and very low level patients versus all other patients who did not receive matching target drugs. H, OS of patients separated by application of matching targeted drug for very high priority level patients versus high, moderate, and intermediate level patients versus borderline, low, and very low level patients versus all other patients who did not receive matching target drugs.