Abstract 5413: Terry Fox PRecision Oncology For Young peopLE (PROFYLE): A Canadian precision medicine program for children, adolescents and young adults with hard-to-treat cancer
Authors: Grover Stephanie A. , Berman Jason N. , Chan Jennifer A. , Deyell Rebecca J. , Eisenstat David D. , Fernandez Conrad V. , Grundy Paul E. , Hawkins Cynthia , Irwin Meredith S. , Jabado Nada , Jones Steven J. , Moran Michael , 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: September 2020

Introduction: Over 4300 children, adolescents, and young adults (CAYA) are diagnosed with cancer each year in Canada, 1/3 of whom will have refractory or metastatic disease or will relapse with a very poor prognosis. Most CAYA cancer survivors suffer significant late effects that impose an enormous burden to them, their family and the health care system. To address this urgent medical and socioeconomic need, a pan-Canadian collaborative program, PRecision Oncology For Young peopLE (PROFYLE), was created with the objective to develop and implement the first Canadian precision oncology pipeline providing access to tumour molecular profiling with the aim of identifying novel targeted therapeutic options in a clinically relevant timeframe for CAYA with hard-to-treat cancer.

Design: Prior to PROFYLE, 3 programs (Personalized Oncogenomics Project (POG), SickKids Cancer Sequencing Program (KiCS), and Personalized Targeted Therapy in Refractory or Relapsed Cancer in Childhood (TRICEPS)) constituted the bulk of childhood precision oncology efforts in Canada. PROFYLE was designed to unite and build upon them, and consists of interconnected nodes including: genomics/bioinformatics, proteomics, cancer modeling, biomarkers, biobanking/data repositories, therapeutics/clinical trial design and biomedical ethics; unified by a shared governance structure. There are 16+ institutions in the PROFYLE consortium. The PROFYLE profiling strategy consists of initial reporting from a &gt;800 cancer gene panel, followed by whole genome (paired germline/cancer samples) and whole transcriptome analyses. Eligibility criteria: ≤29y; treatment at a Canadian oncology center; diagnosis with a hard-to-treat cancer. Profiling results are reviewed by multidisciplinary Molecular Tumour Boards. A patient-specific molecular research report including summary of results and recommendations (actionable finding, potential targeted therapies, any open clinical trials which the patient may be eligible for, change of diagnosis, and/or referral for genetic counselling) is provided to the treating oncologist.

Results: To date, 644 patients have taken part in PROFYLE (n=338) and POG, KiCS, TRICEPS. For the first 100 participants, cancer diagnoses include 43 sarcomas, 23 CNS tumors, 10 leukemia and lymphomas, 10 neuroblastoma and 14 other rare cancers. At study entry, 48% had not yet relapsed, 40% 1 relapse, 10% 2 relapses, and 2% 3+ relapses. 13 had a cancer-predisposing germline mutation and 82 had at least one potentially actionable somatic alteration. The most commonly mutated genes/pathways included TP53, CDNK2A/B, FGFR, MYC, and FLT1/3/4. 82% had results/recommendations from the MTB that informed a medical decision to alter diagnosis, prognosis, or treatment of their disease. In 71%, management recommendations were provided. Analyses of the complete dataset will be presented at the meeting.

Conclusion: The goal of developing a national precision oncology pipeline has been realized through the establishment of the PROFYLE initiative. PROFYLE continues to grow through increased recruitment, additional institutions, contribution of new knowledge to the field of precision oncology, improving access to clinical trials for CAYA patients, and advocacy and partnerships on local, national and international scales.

Citation Format: Stephanie A. Grover, Jason N. Berman, Jennifer A. Chan, Rebecca J. Deyell, David D. Eisenstat, Conrad V. Fernandez, Paul E. Grundy, Cynthia Hawkins, Meredith S. Irwin, Nada Jabado, Steven J. Jones, Michael Moran, 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. Terry Fox PRecision Oncology For Young peopLE (PROFYLE): A Canadian precision medicine program for children, adolescents and young adults with hard-to-treat cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5413.