Abstract 1435: Cabozantinib for relapsed neuroblastoma: Case series from one academic medical center
Authors: Michael P. Perisa, Keri Streby, Mark Ranalli, Micah A. Skeens, Nilay Shah
Journal: Cancer Research (2020)

Abstract Neuroblastoma represents 7% of pediatric cancers in the United States but disproportionately 15% of pediatric cancer-related deaths.1 For patients with high-risk disease, as determined by anatomic, histologic, clinical and molecular staging, aggressive multimodal therapy results in 5-year overall survival of 50-65%.2 Outcomes for relapsed neuroblastoma are worse, with 10% 2-year event free survival and 20% 4-year overall survival.3 These data emphasize the necessity of novel therapeutic approaches for relapsed neuroblastoma. Cabozantinib is a multitargeted tyrosine kinase inhibitor (TKI) approved by the US Food and Drug Administration (FDA) for use in adults for medullary thyroid cancer,4 renal cell carcinoma,5 and hepatocellular carcinoma.5 Cabozantinib is effective preclinically against neuroblastoma tumor cells alone and in combination therapies,6 and it has been shown to be safe and tolerable in a phase I study for pediatric cancers.7 Given these data, we used cabozantinib in four patients with relapsed neuroblastoma for whom other therapeutic options were not available. We report the outcomes of these patients with advanced neuroblastoma treated with cabozantinib, including use of a novel liquid formulation with clinical evidence of pharmacologic activity. 1) Kholondenko, I., Kalinovsky, D., Doronin, I., Deyev, S., Kholodenko, R. Neuroblastoma Origin and Therapeutic Targets for Immunotherapy. Journal of Immunology Research. 2018;1-252) Tolbert VP, Matthay KK. Neuroblastoma: clinical and biological approach to risk stratification and treatment. Cell and Tissue Research. 2018; 372(2):195-2093) London, WB., Bagatell, R., Weigel, BJ., Fox, E., Guo, D., Van Ryn, C., Naranjo, A., Park, JR. Historical Time to Disease Progression and Progression-Free Survival in Patients With Recurrent/Refractory Neuroblastoma Treated in the Modern Era on Children's Oncology Group Early-Phase Trials. Cancer. 2017;4914-49234) INDICATIONS AND USAGE COMETRIQ Is Indicated for the Treatment of Patients with Progressive, Metastatic Medullary Thyroid Cancer (MTC). Dosage Adju; 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208692s003lbl.pdf5) Cabometyx® (Cabozantinib) Tablets (2019) US Prescribing Information.; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208692s0031bl.pdf6) Zhang, L., Scorsone, K., Woodfield, S., Zage, P. Sensitivity of neuroblastoma to novel kinase inhibitor cabozantinib is mediated by ERK inhibition. Cancer Chemother Pharmacol. 2015;76:977-987 7) Chuk, M., Widemann, B., Minard, C., Liu, X., Kim, A., Bernhardt, M., Kudgus, R., Reid, J., Voss, S., Blaney, S., Fox, E., Weigel, B. A phase I study of cabozantinib in children and adolescents with recurrent or refractory solid tumors, including CNS tumors: Trial ADVL1211, a report from the Children's Oncology Group. Pediatr Blood Cancer. 2018;65:1-7 Citation Format: Michael P. Perisa, Keri Streby, Mark Ranalli, Micah A. Skeens, Nilay Shah. Cabozantinib for relapsed neuroblastoma: Case series from one academic medical center [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 1435.