Systematic review of clinical drug development activities for neuroblastoma from 2011 to 2020

Abstract

Background Understanding the landscape of clinical trials for patients with neuroblastoma may inform efforts to improve drug development. Procedure We evaluated therapeutic trials for patients with neuroblastoma from 2011 to 2020 in our search using clinical trial information from ClinicalTrials.gov, Clinicaltrialregister.eu, PubMed, and American Society of Clinical Oncology (ASCO) annual meeting collection. Trends in trials and treatments over time were evaluated qualitatively. Results A total of 192 trials met inclusion criteria. A median of 20.5 trials were started per year, which was stable over time. There were 87 (45%) phase 1, 100 (51%) phase 2, and only five (2.6%) phase 3 trials. The median time to completion was 4.9 years for phase 1 and 2 trials (no phase 3 trials reported as completed during the study period). In all, 34% of trials were international, while 20% of trials were intercontinental. Eighty‐nine percent of nonmyeloablative trials included at least one novel agent. 48% of these trials studied combination therapies, and 86% of these combinations included conventional chemotherapy. Among 157 trials that included a targeted agent, 78 targets were identified, with GD2 being the primary target under investigation in 16.7% of these trials. Only eight trials were included in regulatory decisions, which led to European Medicines Agency (EMA) or Food and Drug Administration (FDA) approval for neuroblastoma. Conclusions The large number of trials initiated per year, the range of targets, and the rate of intercontinental collaboration are encouraging. The paucity of late‐stage trials, the prolonged trial duration, and relative lack of combination studies are major causes of concern. This work will inform future drug development for neuroblastoma.

The Role of Kdm5d in the Development of Chemoresistance to Cisplatin Through Cul4a in Neuroblastoma

“…The combination of clinical and genetic factors allows strati cation of patients into very low, low, intermediate, and high-risk groups (53). Highrisk neuroblastoma (HRNBL) is characterized by the development of acquired chemoresistance (54). To the best of our knowledge, there is currently no information about the role of KDM5D in NBL and the contribution of KDM5D to CDDP-chemoresistance.…”

Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development

“…To classify patients in risk groups, COG employs post-surgical clinical information [ 12 , 13 , 14 ] and INRG uses pre-treatment tumor imaging and clinical criteria, including MYCN amplification status [ 15 ]. Even with multiple staging systems in place, there is room for development, especially among high-risk patients whose long-term survival rate is only around 50% [ 16 , 17 , 18 ]. Furthermore, a substantial proportion of high-risk patients experience a range of side effects due to the high toxicity of conventional chemotherapy.…”

“…Furthermore, a substantial proportion of high-risk patients experience a range of side effects due to the high toxicity of conventional chemotherapy. Thus, more detailed stratification systems and the identification of valuable biomarkers are needed to make targeted therapies available for NB patients, providing more effective and less harmful treatment options [ 17 , 18 ].…”

Do we need more clinical trials?

“…In this issue, Nader et al 1 . investigated the international achievements for neuroblastoma trials in their study: Systematic review of drug development activities for neuroblastoma from 2011 to 2020 .…”

“…In this issue, Nader et al 1 investigated the international achievements for neuroblastoma trials in their study: Systematic review of drug development activities for neuroblastoma from 2011 to 2020. Their approach was straightforward: they evaluated therapeutic trials for patients with neuroblastoma as registered on https://clinicaltrials.…”