Abstract A41: TRICEPS: A feasibility study of personalized targeted therapy in relapsed/refractory childhood cancers

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-03, Vol.76 (5_Supplement), p.A41-A41
• Main Authors: Langlois, Sylvie, Healy, Jasmine, Lajoie, Mathieu, Dumoucel, Sophie, Khater, Fida, Sontag, Thomas, St-Onge, Pascal, Beaulieu, Patrick, Bittencourt, Henrique, Soglio, Dorothée Dal, Carret, Anne-Sophie, Cellot, Sonia, Champagne, Josette, Duval, Michel, Krajinovic, Maja, Leclerc, Jean-Marie, Patey, Natalie, Piché, Nelson, Samson, Yvan, Teira, Pierre, Marzouki, Monia, Sinnett, Daniel
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.PEDCA15-A41

In Canada, about 1500 pediatric cancers are diagnosed each year. Despite improvements in risk-stratified treatments, around 20% of childhood cancer patients do not respond to current therapies and ultimately succumb to their disease, urging the need for new and more effective therapeutic approaches. Personalized targeted therapy (PTT) based on next generation sequencing (NGS) may be a key component to increase cure rates and decrease treatment-related morbidity and mortality. To assess the feasibility of performing PTT clinical trials in the context of childhood cancers, a pilot study is currently underway at the Sainte-Justine UHC, Montreal, where 30 relapsed or refractory cancer patients (aged 0-21 years) are being recruited over a 2 year period and offered in-depth genomic and transcriptomic investigation to identify patient-specific alterations. This pilot study will allow us to determine the number of children with cancer who are suitable candidates for targeted therapy, to determine the number and type of driver mutation(s) found in the recurrent or refractory childhood cancers, to determine the number of cancer patients who harbor actionable driver mutation(s) that can be targeted with a Health Canada/FDA approved targeted drug and to assess the feasibility of going from biopsy to a detailed tumour analysis report within a clinically-relevant timeframe. Thus far, sixteen patients have been recruited in this study between April 2014 and July 2015. Study subject accrual has been successful with 100% compliance. Eight patients have undergone extensive genomic investigation in a real-time manner. We identified clinically relevant genomic alterations (singe nucleotide variants or structural variations) that can be used to inform clinical management for 8/8 of these patients. Patient screen failures occurred due to benign tumor biopsies, necrotic tumor tissue or low tumor purity, resulting in suboptimal DNA/RNA quantity or quality for NGS. Identified relapse-specific mutations allowed follow up of minimal residual disease, particularly post-transplant for relapsed leukemia cases, influenced patient management and revealed alternative therapeutic options for future personalized targeted therapy. This feasibility study shows that PTT based on NGS technology is a useful approach that could be implemented in the clinic within a foreseeable future to guide treatment of relapsed or refractory childhood cancer patients. The following step toward translating our