Investigational drugs for nasopharyngeal carcinoma

ABSTRACT

Introduction: Nasopharyngeal carcinoma (NPC) is endemic to Southern China and Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole exome and genome sequencing (WES, WGS) studies of NPC have reported several actionable therapeutic targets, and that the mutational load of NPC maybe comparable to that of squamous head and neck cancer. These unique biological characteristics have been exploited as potential targets and a wide range of investigational drugs are being investigated in clinical trials.

Area covered: This review focused on the latest clinical development of the most promising classes of investigational agents in the treatment of advanced NPC. These include inhibitors of tumor angiogenesis, kinase signaling pathways and immunotherapy.

Expert opinion: Checkpoint inhibitors and EBV-specific T-cell therapy have shown promising activity in early phase clinical trials, and are being further evaluated in randomized studies. For patients whose tumors express genetic alterations that are known to predict response to kinase inhibitors, novel trial designs such as an ‘Umbrella’ study may be considered given the abundance of targeted agents that are now available for clinical evaluation. It is envisioned that regulatory approval for new drugs for advanced NPC will occur in the near future.

KEYWORDS:

• Nasopharyngeal carcinoma
• immunotherapy
• angiogenesis
• signaling inhibitors

Article highlights

• Non-keratinizing nasopharyngeal carcinoma is associated with Type II Epstein Barr Virus latent infection, dense lymphocytic infiltration and high expression level of inhibitory checkpoint proteins including programmed cell death receptor and ligand 1. These characteristics provide ideal targets for novel immunotherapeutic approaches, some of which are currently under phase III evaluation.

• Whole exome/genome sequencing studies have found a relatively low but distant expression of genetic alterations in the ErbB-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway that may be associated with response to kinase inhibitors. The high prevalence of CCDN1 alterations, nuclear factor kappa-B and epigenetic dysregulations may also provide exploitable targets for preclinical and clinical evaluation in NPC.

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Acknowledgment

We would like to dedicate this review to our late colleague Dr. SF Leung, for his significant contribution to research and treatment of NPC.

Declaration of interest

B. B. Y. Ma has been on the advisory board for Merck Sharp and Dohme (MSD), Bristol Myers Squibb (BMS), Merck Serono, Novartis, Hoffman La Roche, Boerhinger Ingelheim. A. T. C. Chan and E. Hui have been on the advisory board for Merck Sharp and Dohme (MSD), Bristol Myers Squibb (BMS). The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper was not funded.