Emerging and investigational therapies for neuroblastoma

ABSTRACT

Introduction: Treatment for children with clinically aggressive, high-risk neuroblastoma remains challenging. Less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities. Here, we review new and evolving treatments that may ultimately improve outcome for children with high-risk neuroblastoma with decreased potential for late adverse events.

Areas covered: New strategies for treating high-risk neuroblastoma are reviewed including: radiotherapy, targeted cytotoxics, biologics, immunotherapy, and molecularly targeted agents. Recently completed and ongoing neuroblastoma clinical trials testing these novel treatments are highlighted. In addition, we discuss ongoing clinical trials designed to evaluate precision medicine approaches that target actionable somatic mutations and oncogenic cellular pathways.

Expert opinion: Advances in genomic medicine and molecular biology have led to the development of early phase studies testing biologically rational therapies targeting aberrantly activated cellular pathways. Because many of these drugs have a wider therapeutic index than standard chemotherapeutic agents, these treatments may be more effective and less toxic than current strategies. However, to effectively integrate these targeted strategies, robust predictive biomarkers must be developed that will identify patients who will benefit from these approaches and rapidly match treatments to patients at diagnosis.

KEYWORDS:

• Neuroblastoma
• immunotherapy
• MIBG
• molecularly targeted drugs
• genomic trials

Article highlights

• Long-term survival rates for patients with high-risk neuroblastoma remain at less than 50% despite intensive, multimodal therapy.

• The Children’s Oncology Group is developing a Phase 3 clinical trial for patients with newly diagnosed high-risk neuroblastoma to evaluate the efficacy of the targeted radiopharmaceutical ¹³¹I-MIBG for patients with ALK- tumors and crizotinib for patients with ALK+ neuroblastoma.

• Multiple agents including biologics, immunotherapies, and molecularly targeted compounds show promise in early phase trials.

• Genomic driven trials have been developed to match patients with actionable tumor mutations with specific targeted agents.

• Robust predictive biomarkers are needed to identify patients that will benefit most from novel therapies.

This box summarizes key points contained in the article.

Declaration of interest

Susan Cohn owns Stock in Array BioPharma (I), Edwards Lifesciences (I), Gilead Sciences (I), LabCorp (I), United Therapeutics (I), Varian Medical Systems (I), Zogenix (I), AstraZeneca, Pfizer, Abbott Laboratories, Antares Pharmaceuticals, Array BioPharma, Auxilium Pharmaceuticals, Avanir Pharmaceuticals, Baxter International, BioReference Laboratories, DENTSPLY International, Dyax, Edwards Lifesciences, Gilead Sciences, Hansen Medical, Jazz Pharmaceuticals, LabCorp, MEDNAX Services, Novavax, OPKO Health, Smith Nephew, Techne, United Therapeutics, Universal Health Services, Varian Medical Systems, Vermillion, WuXi AppTec, Zimmer Holdings and has received travel expenses from Novartis and United Therapeutics. The remaining authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This research was supported in part by the Neuroblastoma Children’s Cancer Society (SLC), the Children’s Neuroblastoma Cancer Foundation (SLC), the Matthew Bittker Foundation (SLC), The Mark Staehely Foundation (SLC), a gift from Brittany and Michael MacRitchie (SLC), NIH Grant Numbers K12CA139160 (MAA), the Cancer Research Foundation (MAA) and the Conquer Cancer Foundation of the American Society of Clinical Oncology (MAA). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.