BACKGROUND: While the poor prognosis for high risk neuroblastoma (HRNB) underscores the need for new treatment strategies, the elucidation of specific biologic subsets of neuroblastoma suggests a way to improve disease management. The identification of agents that target specific molecular pathways associated with the development or progression of diseases holds promise. The hypotheses for this study were that: 1) the incorporation of a targeted therapy, selected based upon upfront genomic interrogation of the tumor, into standardized induction chemotherapy for HRNB is feasible and may increase the PR/CR/VGPR response rate at the end of Induction therapy; and 2) that the addition of DFMO as maintenance therapy during and for 2 years after the completion of immunotherapy is safe and may decrease the relapse rate.

METHODS: A prospective, multicenter feasibility pilot clinical trial in subjects with newly diagnosed HRNB within the Beat Childhood Cancer Consortium. At diagnosis, patients' tumors underwent DNA exome and RNA sequencing which were analyzed within a molecular tumor board to identify the single best drug out of 6 targeted agents to be added to cycles 3-6 of induction chemotherapy. After consolidation with ASCT and radiation, the patients received DFMO along with standard dinutuximab and retinoic acid and DFMO for 2 years after immunotherapy. Patients were evaluated for additional toxicities with the addition of targeted agents and DFMO in addition to induction response.

RESULTS: The pilot study of 20 eligible patients has shown this process to be feasible. To date, 20 patients have completed induction through immunotherapy portions of the study. The combination of targeted agent with chemotherapy was shown to be safe without any unexpected toxicities. Delays experienced between induction cycles were less than 2 weeks and related to surgery, infection, or thrombocytopenia. The induction response demonstrated an 88% CR/VGPR/PR rate, which suggests improvement over historical 80%. In addition, the combination of DFMO with dinutuximab and retinoic acid was well tolerated and safe without additional toxicities.

CONCLUSION: The pilot study of 20 patients has shown the process of sequencing and the addition of a targeted agent to upfront chemotherapy is feasible and safe without any unexpected toxicities.

Citation Format: Jacqeline Kraveka, Valerie Brown, William Ferguson, Genevieve Bergendahl, William Roberts, Jessica Foley, Deanna Mitchell, Javier Oesterheld, Michael Isakoff, Kathleen Neville, Randal Wada, Jawhar Rawwas, Gina Hanna, Abhinav Beeravally Nagulapally, Jeffrey Bond, Jeffrey Trent, William Hendricks, Sarah Byron, Giselle L. Saulnier Sholler. Peds-plan, pediatric precision laboratory advanced neuroblastoma therapy: Molecular guided therapy for high risk neuroblastoma at diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT073.