Abstract 2558: Molecularly matched targeted therapies benefit high risk pediatric cancer patients

Abstract Introduction: Genomic technologies have the potential to transform the paradigm for diagnosing and treating children with cancer. Although druggable alterations are identified in a large fraction of pediatric cancer patients, the extent to which point-of-care genomic testing directly impacts therapeutic outcomes of individual patients in real-world settings is less well-known. A review of patients sequenced through the Precision in Pediatric Sequencing (PIPseq) program at Columbia University Irving Medical Center (CUIMC) was conducted to describe outcomes of patients treated with a molecularly matched targeted therapy (MTT). Methods: Matched tumor-normal whole exome and tumor transcriptome sequencing was conducted in a CLIA-certified laboratory at CUIMC between January 2013 and March 2023 on samples from 373 high risk pediatric cancer patients including those with 50% survival, rare cancers lacking standard therapies, and relapsed/refractory disease. All cases were reviewed at a multi-disciplinary molecular tumor board and reports were transmitted to the electronic health record (EHR). EHR data were reviewed to identify patients who received a MTT. Tumor-specific response and progression-free survival (PFS) among the MTT cohort were investigated. Clinical benefit was further assessed using the Growth Modulation Index (GMI) whereby patients served as their own control. GMI is the ratio of PFS on the MTT therapy to the PFS on the most recent prior therapy. A ratio of /=1. 3 indicates meaningful clinical activity. Results: Thirty pediatric patients (solid tumors, n=5; CNS tumors, n=15; hematologic malignancies, n=10) received a MTT. Median age at sequencing was 11 years, range 10 months-23 years. Median time to MTT from sequencing was 4. 5 months, range 7 days to 19. 2 months. Best overall response included 7 complete responses (23%), 6 partial responses (20%), 5 with stable disease (17%), 10 with progressive disease (33%), and 2 indeterminate due to early death or lack of follow-up during therapy (7%). GMI was calculated for 19/30 patients (63%) ; median GMI=1. 1. 11 patients were excluded due to lack of prior therapy, early death, insufficient follow-up, or lack of progression between prior and targeted therapies. GMI ratios indicated clinical benefit from MTT for 12/19 patients (63%), median GMI=1. 5. Conclusions: Clinical comprehensive molecular profiling for pediatric patients with high risk cancers identified patients who are candidates for MTT. Overall, MTT led to stable disease, partial or complete response, for 60% of patients. Utilizing GMI ratios as an indicator of clinical benefit for select patients provided additional information beyond traditional endpoints. Twelve patients with GMI /=1. 3 experienced improved PFS compared to their most recent prior therapy. These results demonstrate real-world clinical benefit from MTT, supporting molecular profiling of pediatric high risk tumors. Citation Format: Alice Tao, Jovana Pavisic, Jennifer A. Oberg. Molecularly matched targeted therapies benefit high risk pediatric cancer patients abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2558.