Abstract 636: PROFYLE: The pan-Canadian precision oncology program for children, adolescents and young adults with hard-to-treat cancer
Authors: Grover Stephanie A. , Alcindor Thierry , Berman Jason N. , Chan Jennifer A. , Denburg Avram E. , Deyell Rebecca J. , Eisenstat David D. , Fernandez Conrad V. , Grundy Paul E. , Gupta Abha , Hawkins Cynthia , Irwin Meredith S. , Jabado Nada , Jones Steven J. , Moran Michael F. , Morgenstern Daniel A. , Rassekh Shahrad R. , Shlien Adam , Sinnett Daniel , Sorensen Poul H. , Sullivan Patrick J. , Taylor Michael D. , Villani Anita , Whitlock James A. , Malkin David ,   on behalf of the Terry Fox PROFYLE Consortium
Published: July 2021

Background: Over 4300 children, adolescents, and young adults (CAYA) are diagnosed with cancer each year in Canada, 1/3 of whom have refractory/metastatic disease or will relapse. A national collaborative program, PRecision Oncology For Young peopLE (PROFYLE), was created with the goal to develop and implement a pipeline providing access to tumor molecular profiling to identify novel targeted treatment options in a clinically relevant timeframe for CAYA with hard-to-treat cancers.

Design: PROFYLE unites 21 institutions, building upon 3 pre-existing regional pediatric precision oncology programs (Personalized Oncogenomics (POG), SickKids Cancer Sequencing (KiCS), and Personalized Targeted Therapy in Refractory or Relapsed Cancer in Childhood (TRICEPS)). PROFYLE nodes (genomics/bioinformatics, proteomics, modeling, biomarkers, data/biobanking, therapeutics, bioethics, policy, AYA) are unified by a shared governance structure. PROFYLE includes genomic and transcriptomic sequencing of paired germline/cancer fresh/frozen samples. Inclusion criteria: ≤29y; treatment at a Canadian center; diagnosis of a hard-to-treat cancer. Profiling results are reviewed by multidisciplinary Molecular Tumor Boards. A report including a results/recommendations summary of actionable findings (therapeutic, diagnostic, prognostic, cancer predisposition), potential targeted therapy options including available clinical trials, clarification of diagnosis, and genetic counseling referral is provided to the treating oncologist.

Results: To date, &gt;800 CAYA are enrolled in PROFYLE and POG, KiCS, TRICEPS. Cancer diagnoses: 35% sarcoma, 18% leukemia/lymphoma, 14% CNS tumor, 14% neuroblastoma, 19% other. At study entry, 44% of participants had not relapsed, 39% 1 relapse, 14% 2 relapses, and 3% 3+ relapses. 13% had a cancer-predisposing pathogenic/likely pathogenic germline variant, 39% had ≥1 potentially actionable somatic alteration, and 13% had a therapeutically targetable somatic alteration. The most frequent classes of alterations were RAS/MAPK, immune checkpoint, cell cycle, DNA repair, epigenetic, PI3K/AKT/mTOR, RTK. Of clinicians who reported the utility of results, 78% indicated the findings had the potential to inform a medical decision.

Future Directions: We will build on PROFYLE's success by addressing the challenge of real-time availability of target-based therapies through innovative clinical trial strategies incorporating new drugs, off-label use, drug combinations, basket and single patient study designs to enable improved access to therapies for CAYA with actionable molecular targets. We will work on policy-relevant research to facilitate implementation of precision oncology care for CAYA in Canada. We will leverage knowledge developed by PROFYLE thus far by integrating omics, modeling and biomarkers research in the trials being developed.

Citation Format: Stephanie A. Grover, Thierry Alcindor, Jason N. Berman, Jennifer A. Chan, Avram E. Denburg, Rebecca J. Deyell, David D. Eisenstat, Conrad V. Fernandez, Paul E. Grundy, Abha Gupta, Cynthia Hawkins, Meredith S. Irwin, Nada Jabado, Steven J. Jones, Michael F. Moran, Daniel A. Morgenstern, Shahrad R. Rassekh, Adam Shlien, Daniel Sinnett, Poul H. Sorensen, Patrick J. Sullivan, Michael D. Taylor, Anita Villani, James A. Whitlock, David Malkin, on behalf of the Terry Fox PROFYLE Consortium. PROFYLE: The pan-Canadian precision oncology program for children, adolescents and young adults with hard-to-treat cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 636.