Abstract 7891: Real world treatment with molecularly matched targeted therapies in the era of pediatric precision cancer medicine: Gaining ground or inching forward

Abstract Introduction: Children and adolescents diagnosed with relapsed/refractory or high-risk cancer have a poor prognosis and 20% survival rates for those with recurrent disease. Several pediatric precision cancer medicine programs have been established to inform clinical decision making and provide molecularly matched therapeutic options for patients in need. However, the clinical benefit of these therapies in real-world settings is unknown. A review of the literature and patients sequenced through the Precision in Pediatric Sequencing (PIPseq) program at Columbia University Medical Center (CUMC) was conducted to describe outcomes of patients with solid or CNS tumors treated with a molecularly matched targeted therapy (MTT). Methods: PubMed and the CUMC medical record were reviewed between 2013-2025. Patient-level molecular and treatment data were extracted for those diagnosed with high-risk or relapsed/refractory disease. Clinical benefit rate (CBR) (percent complete response (CR), partial response (PR), and stable disease (SD) for /= 6 months) was evaluated. Progression free (PFS) and overall survival (OS) differences were assessed using the log-rank test. Results: 20 studies and 29 PIPseq patients were identified. 233 CNS and 394 solid tumor (ST) patients were included. 40% (CNS), 23% (ST) and 30% overall derived clinical benefit. Patients with low grade glioma had the highest CBR (69%, n = 36) and medulloblastoma had the lowest CBR (20%, n = 20). CBR for the largest CNS cohort, high grade glioma, was (25%, n = 122). CBR for select ST subtypes were 16% (adrenal, n = 81), 11% (osteosarcoma, n = 65), 16% (rhabdomyosarcoma, n = 55) and 12% (Ewing sarcoma, n = 33). Kaplan-Meier survival analysis was conducted to compare survival distributions across treatment categories, MTT monotherapy, multi agent MTT, and MTT+chemotherapy. By treatment category, median PFS/OS for CNS patients (n = 166/138) were 5.5/32.1, 14/32.2, and 4.8/24 months, respectively. Log-rank tests indicated a significant PFS/non-significant OS difference, X2(2) = 7.45/1.12, p = .025/.571 with an estimated median follow-up of 28/32.1 months. Median PFS/OS times for ST patients (n = 263/179) by treatment category were 4.2/11.6, 1.7/32.3, and 4.1/13.7 months, respectively with non-significant differences in survival, X2(2) = 4.1/1.72, p = .129/.423. The estimated median follow-up was 22.8/28.2 months. Conclusions: Overall, 30% of patients treated with MTT derived clinical benefit. There was a significant difference in PFS but not OS for CNS patients with multiagent MTT yielding the longest PFS and OS compared to MTT monotherapy or MTT+chemotherapy. Treatment modality did not reveal a significant difference in survival for ST patients. Longer follow up beyond 2 years is needed to assess survival in pediatric patients treated with MTT. Citation Format: Jennifer A. Oberg, Jack Boublik-Whiteley. Real world treatment with molecularly matched targeted therapies in the era of pediatric precision cancer medicine: Gaining ground or inching forward abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7891.